In mid-1972, Studd joined the World Wide Wrestling Federation under the ring name "Chuck O'Connor", facing wrestlers such as Chief Jay Strongbow and Gorilla Monsoon. On September 12, 1972, Studd unsuccessfully challenged Pedro Morales for the WWWF World Heavyweight Championship. Later that month at Showdown at Shea, Studd lost to El Olympico by disqualification. He left the WWWF in February 1973.
In 1976, Studd returned to the World Wide Wrestling Federation, where he donned a mask and performed as "Executioner #2", teaming with Executioner #1 as The Executioners. On May 11, 1976, The Executioners defeated Louis Cerdan and Tony Parisi to win the WWF World Tag Team Championship. They held the championship until October 26, 1976, when they were stripped of the titles after a third Executioner interfered in a title defense. Studd left the WWWF once more in early 1977.
Studd jumped back to the World Wrestling Federation in late 1982, and was paired with manager "Classy" Freddie Blassie. Studd quickly became a monster heel, adopting a gimmick of bringing a stretcher to the ring and beating his opponents so badly they would be taken out on the stretcher.
While Studd became a top challenger for the WWF World Championship, held by Bob Backlund, it was his feud with the 7'4", 520 pound André the Giant over who was professional wrestling's 'true giant' that earned him main event status. Studd and Blassie had issued a "Bodyslam Challenge," offering $10,000 (and later, $15,000) to any wrestler that could slam him before boasting that he (Studd) could not be slammed. After several wrestlers were unsuccessful in answering Studd's challenge, Andre accepted and was about to slam Studd before Blassie attacked Andre from behind (as Studd grabbed the ring ropes to prevent himself from being slammed). The Andre-Studd feud raged throughout 1983 and Andre got the upper hand and slammed Studd several times, once with enough force to collapse the entire ring. Several times, the two met inside a steel cage, where André not only slammed Studd, but used a sitdown splash from the top rope onto his chest to knock him out. Despite this, Studd began declaring himself the "True Giant of Wrestling," all while continuing to insist he could not (and had never been) slammed. By 1984, with his feud with Andre still raging, Studd was challenging then-new champion Hulk Hogan for the title; Hogan was also successful on several occasions in slamming Studd.
In late 1984, Studd was also paired with Bobby "The Brain" Heenan, who helped take the André-Studd feud to new heights. This happened during a televised tag team match on WWF Championship Wrestling featuring Studd and fellow Heenan Family member Ken Patera against André the Giant and S.D. Jones. The match ended by disqualification after persistent rule-breaking by Studd and Patera, who attacked André afterwards and cut his hair with Vince McMahon and Bruno Sammartino claiming on commentary that they were raping André of his dignity. André set out for revenge and accepted Studd's challenge to a "$15,000 Bodyslam Challenge" match at the first WrestleMania, whereby if Andre failed to slam Studd before the time limit (or Studd managed to slam Andre), André would be forced to retire from wrestling. André dominated their WrestleMania match at Madison Square Garden and won by slamming Studd.
After WrestleMania, Studd formed an alliance with fellow Heenan Family member, 468 lb King Kong Bundy. The two attacked André at a WWF TV card in Toronto in the summer of 1985, injuring Andre's sternum. The Studd-Bundy alliance and André continued to feud for the rest of that year and into 1986, with Andre often recruiting faces such as Hulk Hogan, Tony Atlas, Junkyard Dog and Hillbilly Jim to team with him. Studd participated in the well-publicized 20 man over-the-top battle royal that took place in the Chicago segment of WrestleMania 2 and featured in a memorable pre-match interview with "Mean" Gene Okerlund and then Atlanta Falcons player Bill Fralic, with Studd telling Fralic he had no business in professional wrestling and Fralic repeatedly calling Studd "Dudd". The invitational battle royale also featured stars from the National Football League. Although André the Giant was also in the match, Studd set his focus on eliminating Fralic and fellow football player William "The Refrigerator" Perry. Studd successfully eliminated Perry during the match, only to have Perry to eliminate Studd while the two were shaking hands. André went on to win the battle royale.
The Andre-Studd feud took on a new dimension in 1986, when—in the wake of Andre's increasing health problems related to gigantism and acromegaly, a storyline was developed to have André compete in a tag team called The Machines. The "Machines" angle began when André failed to show up for a number of tag team matches against Bundy and Studd. Bobby Heenan successfully campaigned to get André suspended, only for André to reappear shortly thereafter in a mask and billing himself as a Japanese wrestler called the Giant Machine. Studd, along with Bundy and Heenan, insisted that Andre and the Giant Machine were one and the same, and set out to prove their point by vowing to unmask the Giant Machine during a series of tag team matches; the Giant Machine's partners included Blackjack Mulligan (as "Big Machine") and Ax (as "Super Machine") with Studd and Bundy saying in interviews that they knew who The Machines were. However, neither Studd, nor Bundy or Heenan, were able to unmask The Machines and their true identities remained a secret.
The Bundy-Studd team also feuded with other established WWF tag teams in 1986, including The Islanders (Haku and Tama), and contended for the WWF Tag Team Championship held by The British Bulldogs (Davey Boy Smith and the Dynamite Kid). During a televised match in late 1986, Studd and Bundy began arguing after they lost a match to the Bulldogs, and although that seemed to foreshadow a feud between the two, nothing ever came of it. Studd's last match during his original 1980s WWF run came on the November 15, 1986, episode of WWF Superstars of Wrestling, where he teamed with Bundy to defeat The Machines (a match that did not involve the Giant Machine).
After retiring for two years, Studd announced his return to the WWF on the Brother Love Show in December 1988. An elated Bobby Heenan appeared on the set to welcome Studd back to the Heenan family. However, with Heenan now also managing his old adversary André the Giant, Studd rejected the offer and ran Heenan off the Brother Love set, thus turning face.
Studd went on to feud with several members of the Heenan family, including André who had turned heel during Studd's absence and Haku (one of the few wrestlers who could bodyslam Studd). Studd won the 1989 Royal Rumble in Houston, which many consider to be the crowning achievement in his WWF career. Studd then served as a special guest referee in the match between Jake "The Snake" Roberts and André at WrestleMania V in Atlantic City. Studd and André had several words with each other both before and during the match and eventually disqualified his nemesis after the giant attacked him from behind. Studd's last match with the WWF was June 4, 1989, with Hillbilly Jim wrestling in Studd's place later that month. Studd quit the WWF soon after.
Studd passed away on March 20, 1995. Shortly after his death, he was inducted into the WCW Hall of Fame.
In 2004, Studd was also posthumously inducted into the WWE Hall of Fame.