In 1986, Blayze started wrestling in the American Wrestling Association (AWA) feuding with Sherri Martel as Madusa Miceli. After Martel left the AWA, she replaced her as "Mr. Magnificent" Kevin Kelly's manager, who often teamed with Nick Kiniski as "The Perfect Tag Team". In a tournament final, she won the AWA World Women's Championship over Candi Devine on December 27, 1987. At that time, Madusa also began managing the AWA World Heavyweight Champion Curt Hennig. She later lost the title to Wendi Richter on November 26, 1988. Hennig and Madusa joined the Diamond Exchange, a stable led by Diamond Dallas Page that included Badd Company. With Badd Company, she faced the team of the Top Guns (Ricky Rice and Derrick Dukes) and Wendi Richter at the only AWA pay-per-view SuperClash III. Both Badd Company's Tag-Team Title and Wendi Richter's AWA World Women's Championship were on the line, but since Richter pinned Miceli, Badd Company retained the championships.
She then went to WCW in 1991 and helped Paul E. Dangerously form his Dangerous Alliance. She acted primarily as Alliance member Rick Rude's valet. On October 25, 1992, Dangerously kicked her out of the Dangerous Alliance at Halloween Havoc. She, however, defeated him by count-out on November 18, 1992 at the Clash of the Champions.
In 1993, the WWF reinstated its Women's Championship, a title that had been vacant since 1990, and Madusa was brought in by the company to revive the women's division. She debuted under the ring name Alundra Blayze. She wrestled in a six-woman tournament to crown a new Women's Champion, and in the finals, she pinned Heidi Lee Morgan on December 13 to win the title. In mid-1994, Bull Nakano joined the WWF roster and began feuding with Blayze. Blayze defeated Nakano at SummerSlam, but lost the belt to her on November 20, 1994 in Japan. Five months later on April 3, 1995, Blayze regained the title from Nakano on an edition of Monday Night Raw. As part of the storyline, immediately following the win, she was attacked by Bertha Faye, who broke her nose. She returned to the ring in August 1995, losing the Women's Championship to Faye at SummerSlam on August 27. Two months later, she won the title a third time, defeating Faye on October 23. In December, due to financial troubles the WWF was having at the time she was released from her contract and was stripped of the title following her jump to rival company World Championship Wrestling, and the WWF Women's Championship remained vacant until 1998.
In December 1995, Blayze signed with WCW, and as part of a storyline by booker Eric Bischoff, showed up on WCW Monday Nitro on December 18, where she threw the WWF Women's Title belt into a trash can. Blayze immediately began using the Madusa name again. Upon her debut she attacked Sherri Martel during her wedding to Col. Robert Parker. She had a match the following Monday on Nitro against Sherri Martel which she lost. After that, the company brought in Bull Nakano to feud with her; they battled in a match at Hog Wild in August 1996. Due to pre-match stipulations, Madusa was allowed to destroy Nakano's motorcycle after the match.
The company then decided to establish the WCW Women's Championship, but Madusa lost to Akira Hokuto in the finals of the tournament to crown the first champion on December 29 at Starrcade. On June 15, Hokuto retained the title against Madusa at The Great American Bash in a Title vs. Career match. The latter then took a nearly two-year hiatus from the company.
Madusa returned to WCW in April 1999 as part of Randy Savage's faction Team Madness with Gorgeous George and Miss Madness. After that storyline ended, Madusa entered into a tournament for the WCW Championship, but she was defeated and eliminated from the tournament. She was later re-entered into the tournament in a match against Evan Karagias, but was eliminated the next week. After her elimination, Madusa put all her focus on managing Karagias. After Karagias won the WCW World Cruiserweight Championship at Mayhem, he was found flirting with Spice of the Nitro Girls. At Starrcade, however, Spice gave Karagias a low blow during the match, and Madusa pinned him to become the first female ever to win the WCW World Cruiserweight Championship. Spice then aligned herself with Madusa and became her manager for a short time.
In January 2000, Madusa developed a rivalry with Oklahoma. In a farcical Evening Gown match on an episode of WCW Thunder on January 12, Madusa defeated Oklahoma by stripping off his dress, but he attacked her after the match. She eventually lost the Cruiserweight belt to Oklahoma at Souled Out on January 16, 2000.
Before WCW's collapse, she engaged in a brief feud with Torrie Wilson and Shane Douglas, who defeated her and partner Billy Kidman at Fall Brawl in a Mixed Tag Team Scaffold match. Madusa took a big bump during this match and wasn't seen again on WCW TV. She left the company soon after.
On March 2, 2015, it was announced that Madusa would be inducted into the WWE Hall of Fame class of 2015, under her Alundra Blayze moniker. Following her Hall of Fame induction, she made a special appearance during the WrestleMania 31 event the following day on March 29, along the other Hall of Fame inductees.
Alundra Blayze was announced as an entrant into the battle royal for a women's championship opportunity at WWE Evolution, marking a return to the ring after an 18 year hiatus, however she was eliminated by Nia Jax.
On July 22, 2019, Alundra Blayze appeared as a heel and attacked 24/7 Champion Candice Michelle, after which she captured the title from Candice by forcing her to submit, with Melina acting as the official, becoming the third woman to win the title, while also becoming the first individual to win the title via submission. She also became the second woman to hold both the WWE Women's Championship and the 24/7 Championship. She later attempted to toss the 24/7 Championship into the trash (similar to when she did the same to the WWF Women's Championship in 1995), only to instead sell the title to WWE Hall of Famer Ted DiBiase.
Blayze would also appear in WWE on the July 26, 2022 episode of NXT, in a backstage segment with Roxanne Perez and McKenzie Mitchell, announcing a fatal four-way elimination match for the vacant NXT Women’s Tag Team Championship. On January 23, 2023, she appeared backstage during Raw is XXX, celebrating the thirtieth anniversary of Monday Night Raw.
Blayze inducted Bull Nakano into the WWE Hall of Fame class of 2024.