In 1976, Hansen made his debut for the World Wide Wrestling Federation (WWWF) and only two months after he began competing for the company, he began feuding with the WWF Heavyweight Champion Bruno Sammartino over the title. During a title match, Hansen broke Sammartino's neck while they were wrestling and it was from this incident that both Hansen and promoters claimed that Sammartino's injury came about from the enormous power of his lariat. After Sammartino recovered, Hansen faced him for the WWWF Heavyweight Championship once again, but was unsuccessful. He left the promotion soon after. He returned in 1980, rekindling his feud with Sammartino and facing Pedro Morales and Andre the Giant on several occasions. He also developed a heated feud with then-WWF Champion Bob Backlund which culminated in a steel cage match at Madison Square Garden.
Hansen competed in the American Wrestling Association (AWA) from 1985 to 1986. He won the World Heavyweight Championship on December 29, 1985, from Rick Martel. On June 29, 1986, he no-showed a title defense against the number one contender Nick Bockwinkel due to disagreements with management, forcing the AWA to default the title to Bockwinkel.
In late 1990, Hansen began appearing in World Championship Wrestling (WCW), feuding with Lex Luger over the WCW United States Heavyweight Championship. On October 27 at Halloween Havoc, Hansen defeated Luger to win the title, ending Luger's record-setting reign at 523 days. On December 16 at Starrcade, Hansen lost the title back to Luger in a bullrope match. Hansen wrestled a match with Vader at the WrestleWar pay-per-view in February 1991. In June, Hansen left WCW. His last WCW match occurred on June 23 in Atlanta.
On April 2, 2016, Hansen was inducted into the WWE Hall of Fame by his rival and friend Vader.