With Daivari as his manager, the unnamed Khali debuted on WWE television as a villain on the April 7, 2006 episode of SmackDown!, attacking The Undertaker and leaving him defenseless during his match with Mark Henry, thus causing a no contest ruling. The following week on SmackDown! he was introduced as The Great Khali and Daivari explained that he finally had a client who would destroy The Undertaker (after Muhammad Hassan and Mark Henry had previously failed). Khali made his in-ring debut on the April 21 episode of SmackDown!, defeating Funaki.
On the May 12 episode of SmackDown!, Khali was John Bradshaw Layfield's hand-picked opponent against World Champion Rey Mysterio, and defeated Mysterio in a squash match. In his match against The Undertaker at Judgment Day on May 21, Khali defeated The Undertaker with a kick to the head after receiving some illegal help from Daivari. Khali continued on a rampage for several weeks, winning handicap matches, beating wrestlers up in a display of power, and mocking The Undertaker's signature pin and victory pose.
Khali then challenged The Undertaker to a Punjabi Prison match at The Great American Bash. However, Khali was not medically cleared to compete in the match and was instead replaced by Big Show, who lost the match despite Khali's interference. After he was medically cleared, Khali was challenged by The Undertaker to a Last Man Standing match at SummerSlam on August 20. The match was moved to the SmackDown! just prior to SummerSlam and was won by The Undertaker, thus giving Khali his first definite loss in WWE.
The Great Khali and Daivari were moved to the ECW brand officially when they made their ECW debuts on the October 31 episode of ECW on Sci Fi, when Daivari defeated "The Reject" Shannon Moore in a very quick match. Afterwards, Moore was manhandled by Khali. Daivari continued his ECW winning streak over the next several weeks with The Great Khali usually following up the contest with a chokebomb on Daivari's opponent. At December to Dismember on December 3, Daivari got a victory over Tommy Dreamer following a roll-up. Dreamer then chased Daivari backstage, but Khali appeared and caught Dreamer, planting him on the steel ramp with a chokebomb.
On the January 8, 2007 episode of Raw, Jonathan Coachman announced that Khali had signed with Raw (without Daivari, who stayed on ECW) and would wrestle John Cena in the main event, which Khali won by disqualification after Cena took a steel chair held by Armando Estrada and hit Khali with it, though after the match he performed a chokeslam on Cena and left the ringside area, leaving Cena prone to an attack by Umaga.
On the February 19 episode of Raw, Khali demanded better competition after easily defeating The Highlanders. Four days later on SmackDown!, Khali interfered in a falls count anywhere Money in the Bank qualifying match between Kane and King Booker by costing Kane the match, leading to a feud which culminated in a match at WrestleMania 23, which Khali won in his first appearance at WrestleMania after slamming Kane with the Khali Bomb and choking him with a hook and chain at the end of the match.
On the April 30 episode of Raw, Khali attacked Edge, Randy Orton and Shawn Michaels (all three top contenders to the WWE Championship at the time) backstage. Khali then attacked WWE Champion John Cena as well, sending a message that he wanted Cena's title. The next week on Raw, Khali defeated Michaels in a number one contender's match for the WWE Championship at Judgment Day. At the event on May 20, Khali lost via submission for the first time when tapping out to Cena's STFU, though Khali's foot was under the rope and went unnoticed by the referee. The next night on Raw, Khali expressed his outrage over the outcome via his newly established translator and manager, Ranjin Singh. At One Night Stand on June 3, Khali lost to Cena after he was hit with an FU off a crane bed, thus marking the first time Khali had been pinned in a singles match.
On the June 11 episode of Raw, as part of the 2007 WWE draft, Khali was drafted to SmackDown! as the brand's first draft pick. In July, Khali began a feud with Batista and the two were scheduled for a match at The Great American Bash. However, because Edge vacated the World Heavyweight Championship due to a legitimate injury, a twenty-man battle royal was held for the title on the July 20 edition of SmackDown!, which Khali won after eliminating both Kane and Batista in one move, thus winning his first World Heavyweight Championship. Khali dominated and defeated both Batista and Kane in a triple threat match at The Great American Bash on July 22. Khali then debuted a new finisher called the Khali Vise Grip (a two-handed clawhold) which he used to wear down Batista, Kane and Ric Flair.
At SummerSlam on August 26, Khali lost by disqualification when he used a steel chair, but retained the title. Khali then began a feud with Rey Mysterio after Mysterio won a championship competition to become the number one contender, leading Khali to apply his Visa Grip on Mysterio on the September 7 episode of SmackDown! until Batista came to the rescue, with SmackDown General Manager Theodore Long informing Khali that he would have to defend the World Heavyweight Championship also against Batista in a triple threat match at Unforgiven on September 16, where Khali's 61-day reign ended after receiving a spinebuster. Khali challenged Batista to a rematch in a Punjabi Prison match at No Mercy on October 7, in which Khali lost by failing to escape the Punjabi cage before Batista.
In late 2007 and early 2008, Khali was put in a program with Finlay, usually trying to assault Hornswoggle, but with Finlay stopping him. Khali participated in an Elimination Chamber match at No Way Out on February 17, which was won by The Undertaker. At WrestleMania XXIV on March 30, Khali participated in a twenty-four man battle royal to determine a challenger for ECW Champion Chavo Guerrero later that evening, but the match was won by Kane. Khali then had a short feud with Big Show, culminating in a match at Backlash on April 27, which Big Show won.
In July, Khali feuded with Triple H over the WWE Championship and on July 25 episode of SmackDown, he won a battle royal also involving Big Show, Jeff Hardy, Montel Vontavious Porter, Mr. Kennedy and Umaga to earn the right to face Triple H at SummerSlam. At the event on August 17, Khali lost to Triple H after receiving a Pedigree. Khali was given another opportunity to win the WWE Championship when he faced Jeff Hardy to gain entry into the championship scramble at Unforgiven on September 7, but Triple H interfered in the qualification match and aided Hardy with a chair shot to Khali, thus helping Hardy win and eliminating Khali from title contention.
Khali invited Johnny Knoxville to attend the October 13, 2008 episode of Raw, where Knoxville was attacked by Khali, Beth Phoenix and Hornswoggle. Khali then took on a more fun persona and became a fan favorite when he and Ranjin Singh hosted the weekly Khali Kiss Cam, where Singh would summon ostensibly random women from the audience to kiss Khali. In May 2009, The Great Khali feuded with Dolph Ziggler, winning by disqualification after Ziggler attacked him with a steel chair. As a result, Khali began coming out to the ring during and after Ziggler's matches, in attempt to gain revenge and to stop Ziggler from cheating. Over the next few weeks, Khali lost to Ziggler by countout and disqualification after Ziggler made it look like Khali hit him with a steel chair. At The Bash on June 28, Khali lost to Ziggler by pinfall after Kane returned and attacked Khali. It was later revealed that Ranjin Singh was Khali's brother, while the feud with Kane resulted in matches at SummerSlam on August 23 and Breaking Point on September 13, both of which Khali lost.
Khali required knee surgery and Kane assaulted him with the ring steps during a match so Khali could have time off. Whilst injured, Khali made a surprise appearance alongside Ranjin Singh, Ozzy Osbourne, and his wife Sharon on the November 2, 2009 episode of Raw as a judge for the Raw's Got Talent segment, in which he hit Chavo Guerrero with a chop. Khali made his official return on the December 14 episode of Raw, teaming with Christian and Kane to defeat Ezekiel Jackson, Vladimir Kozlov and William Regal.
On the April 2 episode of SmackDown, it was announced that Khali would take time off, but he made an appearance as Khaluber (Khali dressed as MacGruber) on the April 19 Raw by teaming up with special guest host Will Forte (as MacGruber) in a handicap match against Vladimir Kozlov, which they won by intentional countout. As part of the 2010 WWE supplemental draft, Khali and Ranjin Singh were both drafted back to the Raw brand. After returning from his hiatus the previous month, Khali was announced by John Cena to be a part of his team along with Bret Hart, Chris Jericho, Edge, John Morrison and R-Truth to face The Nexus at SummerSlam on August 15, but on the August 9 episode of Raw, he was assaulted and injured by The Nexus, thus removing him from the match.
Khali made his return at the 2011 Royal Rumble, but was eliminated shortly by Mason Ryan. On the March 14 episode of Raw, after Khali defeated The Miz by disqualification, Miz assaulted Khali with a steel chair, injuring him. Khali won an interbrand dark match battle royal at WrestleMania XXVII on April 3. On April 26, Khali was drafted back to SmackDown as part of the 2011 supplemental draft. Khali returned on the April 29 episode of SmackDown, talking backstage with Jinder Mahal, who made his WWE debut that night. On the May 2 episode of Raw, Khali dressed up as the Tooth Fairy at The Rock's birthday party. On the May 6 episode of SmackDown, Mahal—unimpressed by how Khali and Ranjin Singh have been partaking in childish activities instead of winning matches—confronted Singh about his mismanagement of Khali. Mahal then interrupted a Khali Kiss Cam segment the following week on SmackDown, slapping Khali twice. On the May 20 episode of SmackDown, Mahal interrupted Khali's match against Jey Uso, which led to Khali leaving the ring to confront Mahal, who then slapped Khali again, which made Khali re-enter the ring, defeat Jey Uso and then assault Jimmy Uso after the match.
On the May 27 episode of SmackDown, after being defeated by Kane, Mahal came out and shoved Ranjin Singh and then Khali used his Vise Grip on Singh, thus forming an alliance with Mahal and acting as Mahal's bodyguard, assaulting Mahal's opponent's after his matches. On the July 1 edition of SmackDown, Ranjin Singh revealed that Mahal was their brother-in-law and that if Khali did not obey Mahal, then he would divorce Khali's sister and put his family back into poverty. On the September 9 episode of SmackDown, Khali and Mahal went against WWE Tag Team Champions Air Boom (Evan Bourne and Kofi Kingston) in a losing effort after Khali pushed Mahal, allowing Kingston to hit his finishing move onto Mahal and after the match, he walked away from Mahal, thus endinng their alliance. On the September 23 episode of SmackDown, Khali defeated Mahal. On the September 30 episode of SmackDown, Khali was defeated by World Heavyweight Champion Mark Henry, who after the match "fractured" Khali's fibula with a steel chair.
On January 29, 2012, Khali returned to WWE at the Royal Rumble as the number fifteen entrant in the Royal Rumble match, eliminating Ezekiel Jackson and Jinder Mahal before being eliminated by Cody Rhodes and Dolph Ziggler. Khali returned on the February 3 episode of SmackDown, saving Justin Gabriel from Rhodes, Hunico and Hunico's bodyguard Camacho, then being announced as the replacement to Mark Henry in the SmackDown Elimination Chamber match for the World Heavyweight Championship at the Elimination Chamber pay-per-view event. At Elimination Chamber on February 19, Khali failed to capture the World Heavyweight Championship after being eliminated first by Big Show. On the March 23 episode of SmackDown, Khali was added to Theodore Long's WrestleMania XXVIII team, but they were defeated by John Laurinaitis' team on April 1. In July, it was announced that Khali was undergoing surgery. Khali returned at the SmackDown tapings on October 16 in a match taped for Saturday Morning Slam.
On the December 26 episode of Main Event, Khali won a 20-man battle royal to become the number one contender to the United States Championship. Khali received his title shot on the January 2, 2013 episode of Main Event, but was defeated by defending champion Antonio Cesaro. On January 27, Khali competed in the 2013 Royal Rumble match, but was eliminated by Daniel Bryan and Kane. In late 2013, Khali began teaming with Santino Marella and resumed being managed by Hornswoggle after they defeated Heath Slater and Jinder Mahal on the September 27 episode of SmackDown, but at Battleground on October 6, they were defeated by Cesaro and Jack Swagger. On January 26, 2014, Khali participated in the 2014 Royal Rumble match, but was eliminated by The Shield.
At WrestleMania XXX on April 6, Khali competed in the André the Giant Memorial Battle Royal, but failed to win. Khali participated in the Intercontinental Championship battle royal at Battleground on July 20, but the match was won by The Miz. On the October 31 episode of SmackDown, Khali was defeated by Rusev in what would be his final match in WWE, as on November 13, his contract expired and he left WWE.
On July 23, 2017, Khali returned to WWE at Battleground as a heel to assist WWE Champion Jinder Mahal in a Punjabi Prison match for the WWE Championship, by preventing Randy Orton from escaping the structure, allowing Mahal to escape and retain the title.
Khali returned on the April 27, 2018 in The Greatest Royal Rumble match, entering at number forty-five, and lasted for less than a minute, before being eliminated by Braun Strowman and Bobby Lashley. It was confirmed on March 24, 2021 that Khali would be inducted into the WWE Hall of Fame.
Khali made an appearance at the WWE Superstar Spectacle event in Hyderabad, India on September 8, 2023, where he stated that he had one final match in him.