Maria competed in the Diva Search in 2004, deciding to enter the contest after seeing an advertisement while watching Raw. Even though she only placed fifth in the contest, she was hired by the company. She stood out in the contest by giving fellow contestant Carmella DeCesare the finger after being eliminated from the contest. Maria was brought on to Raw as a ditzy backstage interviewer and the host of WWE KissCam in November 2004. Her gimmick involved her asking wrong questions, irritating and amusing the roster.
In 2005, Maria began wrestling and was defeated in her first official match on the January 10, 2005 episode of Raw by Christy Hemme in a Lingerie Pillow Fight. On the March 14 episode of Raw, one of Maria's fillings legitimately fell out after she was slapped by Trish Stratus. She also competed in a Fulfill Your Fantasy Diva Battle Royal at Taboo Tuesday for the WWE Women's Championship, but was the first to be eliminated. On November 14, Maria competed in a non-title Diva Battle Royal at the Eddie Guerrero tribute Raw show, where she was one of the last three women left but was eliminated by Melina and Trish Stratus.
On the November 28 episode of Raw, Maria interviewed then-Raw General Manager Eric Bischoff, and asked him whether or not he thought he was going to be fired. He then booked her in a match with Kurt Angle out of spite, and Maria was laid out with the Angle Slam. As a result, one week later, Maria testified in the trial against Bischoff, who was being fired because of his controversial actions as General Manager.
On the January 2, 2006 episode of Raw, Maria was attacked and stripped of her clothes by Vince's Devils (Victoria, Torrie Wilson, and Candice Michelle), but she was saved by Ashley Massaro. During a commercial break that night, Vince McMahon announced a Gauntlet Bra & Panties Match for New Year's Revolution between all five girls. At the event, Maria was the first to enter the Gauntlet match and eliminated Michelle and Wilson before being eliminated by Victoria. The match was ultimately won by Massaro. On the February 6, episode of Raw, Jonathan Coachman announced that Edge and Lita would have fought the mixed team of John Cena and Maria in the main event, and before the match Cena kissed Maria, who came into his locker room to express her nervousness for the competition (despite the kiss, no on-screen romance between the pair was born). Maria scored the victory after a spear meant for Cena hit Lita. On the April 10 episode of Raw, Maria received title match for Mickie James' WWE Women's Championship, but lost. On October 16, Maria won a Fatal Four-Way Bra and Panties match against Victoria, Candice, and Wilson to advance to the semi-finals in a Women's Championship Tournament. Maria, however, lost in the semi-finals to Lita.
On the January 1, 2007 episode of Raw, Maria attempted to interview Kevin Federline, but was instead slapped by Melina. This led to a match between the two later that night, which Melina won. At New Year's Revolution, Maria and Candice ran to the ring during the Women's Championship match between Victoria and Mickie James to stop Melina from interfering, helping James retain the title. In the following weeks she faced Melina in two tag team matches, where she won one. Maria began an on-screen romance with Santino Marella in June. On the November 5 episode of Raw, Marella was confronted by the returning Stone Cold Steve Austin for criticizing his movie, The Condemned. As a part of the storyline, the argument ended as Marella received a Stone Cold Stunner from Austin.
After Ashley Massaro's return in early 2008, Kanellis engaged in backstage segments where Massaro suggested Maria should be on the cover of Playboy. As a part of the storyline, Maria defeated Beth Phoenix on February 18, to "earn the right" to be on the cover of the magazine. During her Playboy cover unveiling, Maria's cover was plastered over with images of Marella. After Marella offered an ultimatum of posing for the magazine or staying with him as a couple, she then broke up with him. Maria, along with Ashley were defeated by Phoenix and Melina at WrestleMania XXIV in a Playboy BunnyMania Lumberjill match. After the match, Maria passionately kissed the Master of Ceremonies, Snoop Dogg. The next night on Raw, Maria wrestled Marella, but the match ended by disqualification. This ended their feud.
As part of the 2008 WWE supplemental draft, Maria was drafted to the SmackDown brand. She made her debut on the August 1 episode of SmackDown by defeating Victoria. On the October 17 episode of SmackDown!, Maria won a "Las Vegas Dice on a Pole" match to become the number one contender for the WWE Divas Championship, but lost for the title against then-champion Michelle McCool. Maria participated in the Raw vs. SmackDown Divas match at Survivor Series, where she eliminated Jillian Hall before her team lost the match. On the December 5 episode of SmackDown!, Maria got an upset victory over the Divas Champion Michelle McCool, but she was defeated by Maryse in a number one contender's match for the title two weeks later. At Armageddon on December 14, Maria was part of the winning team of a Santa's Little Helper tag team match. On the December 26 episode of SmackDown!, she served as a special guest referee in the Divas Championship match between Maryse and McCool, where Maryse became the new champion. After the match, McCool turned heel and attacked Maria, injuring her shoulder.
On the January 23, 2009, episode of SmackDown, Maria returned and attacked McCool during a match. On the February 13 episode of SmackDown, she defeated McCool following interference from Eve Torres. Over the next several weeks, Maria competed in various tag-team matches against McCool, with Maria winning three out of four matches. She also competed at WrestleMania XXV for the "Miss WrestleMania" crown, but was eliminated by Victoria. Throughout June, Maria served as the special guest referee in Diva matches. Maria made her in-ring return on the July 3 episode of SmackDown, teaming with Melina to defeat LayCool (Michelle McCool and Layla). Soon after, she entered into an on-screen relationship with Dolph Ziggler, despite her being a fan favorite and him being a villainous character. At Night of Champions, Maria accompanied Ziggler to his match with Rey Mysterio for the Intercontinental Championship. In the following weeks, Melina implied that Ziggler was cheating on Maria, which Maria did not believe. Maria and Ziggler later broke up on the October 10 episode of SmackDown in a backstage segment, after she cost him his match with John Morrison. Maria then took a brief hiatus from the ring, but returned on the December 4 episode of SmackDown by helping Mickie James fend off an attack by LayCool. She made her in-ring return the following week, teaming up with James to defeat LayCool. On December 14, Maria won the Slammy Award for Diva of the Year, which was voted for by WWE fans.
On the February 12, 2010, episode of SmackDown, Maria began a brief on-screen relationship with Matt Hardy. On February 26, 2010 Maria was released from her WWE contract.
On June 18, 2017, Kanellis returned to WWE alongside her husband Mike Kanellis in his WWE debut at Money in the Bank, establishing the Kanellis couple as heels for the first time in Maria's WWE career. On the July 18 episode of SmackDown, Maria helped Mike defeat Sami Zayn in his WWE debut match. In September, Kanellis went on a leave of absence from WWE, following her pregnancy announcement. On January 22, 2018, at the 25th Anniversary of Raw, a visibly pregnant Maria was honored as part of a segment involving women considered legends that contributed to the company's success, including The Bella Twins (Brie and Nikki), Maryse, Kelly Kelly, Lilian Garcia, Torrie Wilson, Michelle McCool, Terri Runnels, and WWE Hall of Famers Jacqueline and Trish Stratus.
Nine months later, on the October 10 episode of 205 Live, Maria officially made her television return as she interrupted a match between Lince Dorado and Lio Rush, allowing her husband (who debuted on the show) to attack Dorado. Three weeks later, on October 28, in her first match back in WWE in over eight years, Kanellis took part of the first ever all women's pay–per–view, Evolution, where she competed in a battle royal for a future women's championship match but she was eliminated by the eventual winner Nia Jax. Throughout the rest of the year, Kanellis would continue her managerial role as she would accompany her husband Mike to his matches on 205 Live where both would appear regularly. On January 27, 2019, at the Royal Rumble, Kanellis competed in her first women's Royal Rumble match, entering at number 15 and lasting 08:12 minutes before she was eliminated by Alicia Fox. They would not appear on television until the January 29, 2019 205 Live, where Mike would lose to Kalisto.
On the July 1, 2019 episode of Raw, Mike and Maria lost a mixed tag team match against Seth Rollins and Becky Lynch. During the match, Maria revealed she was pregnant with her and Mike's second child. On the July 29 episode of Raw, after Mike had won the WWE 24/7 Championship from R-Truth, he hid from a crowd of male wrestlers in his and Maria's locker room where Maria instructed Mike to lay down so she could pin him and win the title to become the 24/7 Champion, her first title in WWE. The following week, she lost the title back to Mike when he hugged her on the examination table during Maria's OB-GYN appointment.
On April 15, 2020, Kanellis was released from her WWE contract, alongside her husband and multiple other superstars.