In 1981, Orton competed in the World Wrestling Federation. He challenged Bob Backlund for the WWF Heavyweight Championship, winning by count-out (the title can't change of hands by disqualification or count-out). They had a lumberjack match a month later, but Orton was again unsuccessful.
Orton re-joined the WWF in 1984 for what would be the most famous run of his career. He was often addressed as "Ace" Orton by Roddy Piper, and was Piper's bodyguard. His other gimmick, wearing a cast during his matches, stemmed from legitimately having his left forearm broken in a match with Jimmy Snuka at the 1985 event The War to Settle the Score in Madison Square Garden. Although the injury healed in real life, the "cast" gimmick involved Orton—on "doctor's orders"—continuing to wear the cast, claiming the injury had not healed; Orton instead would use the cast to his advantage, striking his opponents behind the referee's back. He won several matches, with the cast and without the cast.
In 1985, Orton was the #1 contender to the WWF Intercontinental Championship, eventually wrestling then-current champion Tito Santana. Orton was successful in winning untelevised matches and events against Santana, but Orton mostly won by either count-out or disqualification. Orton would also be successful in defeating Santana in non-title bouts, but Santana ultimately remained as the champ, and Santana eventually got the upper hand in the feud.
Orton would also engage in a bitter feud with Jimmy Snuka through 1985 and 1986. Orton, just like with Santana, managed to achieve victories over Snuka but mainly in untelevised shows. Just like his feud with Santana, Snuka would get the upper hand in the feud.
Orton was involved in the main event of the very first WrestleMania at Madison Square Garden in 1985, being in the corner of Piper and 'Mr. Wonderful' Paul Orndorff in their match against Hulk Hogan and Mr. T. Orton accidentally cost his team the match after an attempted cheat backfired, resulting in him hitting Orndorff with the cast. Orton also competed in the main event against WWF Champion Hulk Hogan on the premiere episode of Saturday Night's Main Event on NBC broadcast May 11, 1985, which he lost by disqualification due to the interference of Piper. Orton took part in the 1985 King of the Ring tournament on July 8; he fought Paul Orndorff to a double disqualification
Orton remained with Piper for the remainder of 1985, feuding with Orndorff and a variety of partners, such as Hogan, André the Giant, and Bruno Sammartino. In early 1986, Orndorff began wearing a cast as a neutralizer, and the WWF ordered both men to remove their casts. Also in late 1985 and early 1986, Orton challenged Hogan for the WWF Heavyweight Championship; like his matches four years earlier against Backlund, Orton was not successful. On June 30, at a house show held on Bloomington, Minnesota, Orton and Piper surprisingly scored an upset victory over Orndorff and Hogan, albeit by DQ; this event also would be the first time Orton got a victory over Hogan as previous matches between them typically saw Hogan winning.
Orton was dubbed "Boxing" Bob and "Battling" Bob in early 1986 after the cast came off and fought Mr. T at Saturday Night's Main Event, which served as a setup for the Piper-Mr. T match at WrestleMania 2. Prior to WrestleMania 2, "Boxing" Bob Orton defeated Jose Luis Rivera in a boxing match.
Piper and Orton went their separate ways after WrestleMania, with Piper taking a hiatus and Orton in the meantime becoming the bodyguard for Piper's talk-segment successor "Adorable" Adrian Adonis; Adonis had Orton wear a pink cowboy hat. When Piper returned later in 1986 to reclaim his talk show segment (turning face in the process), Orton betrayed his long-time friend, sparking a violent feud between Piper and Orton and his new partners, which typically saw Piper winning. During this time, Orton formed a tag team with The Magnificent Muraco, with the duo managed by Mr. Fuji, and sometimes Jimmy Hart. During their first years as a team, the team of Muraco and Orton was given a fairly decent push, and both were able to easily defeat preliminary wrestlers when not teaming. They appeared at the opening match at WrestleMania III, losing to the Can-Am Connection.
The team of Muraco and Orton also got into a series of matches with The Killer Bees (a team composed of B. Brian Blair and Jumpin' Jim Brunzell). Both teams exchanged victories at televised events, but ultimately the Bees got the upper hand at untelevised events. Referee Danny Davis would usually disqualify the Bees as a part of his heel gimmick. They were notable for being the first team to lose to The Young Stallions (a team composed by Jim Powers and Paul Roma), alongside Tito Santana.
By 1987, the team of Muraco and Orton was clearly stepping down the card. While they were still able to defeat preliminary teams, Orton and Muraco would usually find themselves on the losing end to upper-card teams. Orton and Muraco then eventually started arguing during their matches, which also caused them to lose credibility as a team. This finally led to a match on WWF Superstars of Wrestling where Orton caused him and Muraco to lose a match when Orton kept Muraco from performing a superplex, which was Orton's finishing move. Orton felt offended that Muraco was trying to steal his hold. This led to a brawl between both wrestlers that took place inside and outside the ring. On September 7, 1987, Orton and Muraco finally faced off at a WWF house show. This match ended in a double disqualification. Orton and Muraco faced off during the late months of 1987. By this point, the team was essentially disbanded, with the now-turned face "The Rock" Magnificent Muraco getting the upper hand in the feud. During Orton's feud with Muraco, Mr. Fuji would return to manage Orton (Muraco dumped Mr. Fuji as his manager following his face turn). Orton's last televised match and victory as a whole in the WWF came on October 10, 1987, in a heated victory against preliminary wrestler Siva Afi. Orton's last match with the WWF came on November 7, 1987, where Orton fought preliminary wrestler Sam Houston to a draw in his home state of Missouri. Orton was then released.
In 1989, Orton tried to make a comeback to the WWF, losing to Ted DiBiase in a WWF house show at Springfield, MI on October 11. However no contract was ever offered to him.
On March 30, 1989, Orton made his debut with World Championship Wrestling at a WCW Saturday Night taping in Atlanta, GA and, managed by Gary Hart, defeated Shane Douglas. On the April 1st episode of WCW Saturday Night, it was announced that Orton would be facing Dick Murdoch at the upcoming Clash of Champions VI. The following day at the Clash, Orton defeated Murdoch after Gary Hart interfered. He then went on a house show tour facing mostly preliminary opposition. On April 14 in Milwaukee, WI Orton suffered his first defeat, falling to Mike Justice. Murdoch challenged Orton to a bullrope match after he had interfered in one of Orton's matches, in which Orton defeated Trent Knight. He lost to Murdoch at the 1989 WrestleWar in the bullrope match. Shortly after the match, Orton's manager "Playboy" Gary Hart started brawling with Murdoch, and then Orton attacked Murdoch with the cowbell of the bullrope, and threw him out of the ring, choking him, and attacking the referees that were trying to stop him in the process. After his release, Orton made a one-time appearance at a WCW house show in Kiel, MO, defeating Dutch Mantell.
On February 3, 2005, Bob Orton was announced as a 2005 inductee into the WWE Hall of Fame. In the weeks preceding WrestleMania 21, Orton became entangled in his son Randy's feud with The Undertaker. During an episode of SmackDown!, Orton begged The Undertaker to show mercy on his son in order to distract The Undertaker long enough for his son to sneak into the ring and hit the RKO. At WrestleMania, he (unsuccessfully) interfered in the match between Orton and The Undertaker, striking The Undertaker with his cast. On August 21, 2005, at SummerSlam, Orton interfered in a rematch between Randy and The Undertaker, this time enabling his son to defeat The Undertaker. Orton then began accompanying Randy to ringside during his matches, and teamed with his son at No Mercy on October 9, 2005, defeating The Undertaker in a handicap casket match. The Ortons teamed together once again on the October 28, 2005 episode of SmackDown!, joining forces with Ken Kennedy to face Roddy Piper, Batista, and Eddie Guerrero in a six-man tag team match. The match ended in defeat for the Ortons when Orton succumbed to Piper's sleeper hold. On the December 16, 2005 episode of SmackDown!, Orton disguised himself as one of the Undertaker's druids and carried The Undertaker's signature urn to ringside as The Undertaker came to the ring to confront Randy. Orton remained at ringside after the other druids had left, distracting The Undertaker and enabling Randy to attack him. Orton then handed Randy the urn, which Randy used to knock The Undertaker unconscious. At Armageddon, Orton (still holding the urn) accompanied Randy to ringside for his Hell in a Cell match with The Undertaker. He interfered in the match several times, but was ultimately unable to prevent The Undertaker from delivering a Tombstone Piledriver to both Ortons and then covering Randy for the win. On February 13, 2006, Orton was released from WWE.
Orton made an appearance on the November 15, 2010 episode of WWE Raw as the show went old school, with appearances from past WWE wrestlers, announcers and other on-air personalities. He also appeared on the April 10, 2012 episode of WWE SmackDown and was attacked by Kane (offscreen) who had been feuding with his son Randy at the time. Orton appeared once again on June 18th 2017, at the Money in the Bank pay-per-view, situated in the front row of the crowd along with fellow Hall of Famers Ric Flair and Sgt. Slaughter. During the match between his son Randy and Jinder Mahal, he would be assaulted by the Singh Brothers as they were ejected from ringside; this prompted Randy to attack the Singh brothers. However this distraction proved enough for Jinder to hit Randy with the Khallas for the victory.