Holly first appeared with both World Championship Wrestling and the World Wrestling Federation as Starla Saxton, unsuccessfully challenging Jacqueline for the WWF Women's Championship on an October 1998 episode of Sunday Night Heat and on an episode of the U.K. version of Shotgun.
She debuted in WCW in 1999 as Miss Madness, one of Randy Savage's valets along with Gorgeous George and Madusa. As part of the storyline, this villainous alliance, called Team Madness, would interfere in matches for the benefit of Savage. Eventually, Savage betrayed Miss Madness by firing her from Team Madness along with Madusa after a championship loss. She then became Mona, a fan favorite, who wore a beauty pageant sash, tiara, white gloves, and heels to the ring and wrestled barefoot in a blue cocktail dress. She embarked on mini-feuds with Madusa, Little Jeannie, and Asya. WCW released Mona, however, in August 2000 in a cost-cutting move.
In 2000, she reappeared in the World Wrestling Federation under the name Lady Ophelia, wrestling dark matches and valeting for William Regal.
Ophelia, however, had her first major run in the company as Molly Holly, where she joined her on-screen cousins Bob Holly and Crash Holly. At the time, The Holly Cousins were involved in a feud with T&A (Test, Albert, and manager Trish Stratus). Molly's arrival on the November 6, 2000 edition of Raw started a short feud with Stratus, leading to her first televised victory over Stratus in a six-person intergender tag team match at the Survivor Series. On the November 23, 2000 edition of SmackDown!, Holly using the Molly-Go-Round, defeated Stratus in her first singles match in the WWF. In 2001, Molly formed an on-screen relationship with Spike Dudley, in the midst of their storyline rivalry between her cousins and Spike's brothers (The Dudley Boyz). A subsequent fallout between her and Crash even led to an intergender singles match, with Molly pinning Crash.
In September 2001, Molly dumped Spike to become Mighty Molly, the superhero sidekick of The Hurricane. Molly, however, eventually left The Hurricane to become a full-time solo wrestler, taking his Hardcore Championship after whacking him with a frying pan at WrestleMania X8 on March 17, 2002 in Toronto, Ontario, Canada. She promptly lost it to Christian an hour later after getting a door slammed in her face.
After splitting up with The Hurricane in April 2002, she returned to her previous ring name, Molly Holly. Upon her return to the newly renamed World Wrestling Entertainment (WWE), she drastically changed her look by shortening her trademark blonde hair and darkening it to autumn brown. Holly adopted a villainous, self-righteous prude character, who was appalled by the other WWE Divas continually using their "assets" and degrading themselves. During this gimmick, she would often refer to herself as being "pure and wholesome."
After turning heel, Holly began her first rivalry as a villain with Trish Stratus after she attacked her in a post-match assault on the April 1 episode of Raw, by breaking a paddle over Stratus head. On the April 15, episode of Raw, Holly was defeated by Trish Stratus in a number one contenders match to Jazz's Women's Championship. On the May 6 episode of Raw, Holly was defeated by Terri in a Diva's showdown contest, after wearing a covered swim suit and claiming to have dignity as Terri was dressed with a more revealing swim suit, before attacking her and being stopped by Jerry Lawler. This led to a match between both of them the following week on the May 13 episode of Raw, where Holly emerged victorious. Following this, her feud with Stratus further escalated after Trish provoked Molly by making fun of Molly's large bottom on the June 10 episode of Raw, which led to a match that same night, where Holly defeated Stratus in a non–title match. The rivalry led to a match at King of the Ring on June 23 for Trish's Women's Title, where Molly successfully captured it for the first time after pinning Stratus by hooking her tights. The following night on Raw, Holly teamed up with Jackie Gayda for a tag team match and stated that she finally had brought back dignity to the Women's Title by not being a "tramp who sleeps her way to the top" referring to Stratus, before being defeated by Trish and Linda Miles. On the July 15 episode of Raw, Holly successfully defended her title against Trish Stratus. After multiple intergender tag team matches throughout mid-July, August and early September, including the first intergender tag team tables match between both Molly and Stratus (who started an alignment with Bubba Ray Dudley, who competed along with her), Trish received a rematch for Molly's championship on September 22 at Unforgiven, where she dropped the title back to Stratus. The following night on Raw, Holly tried to regain her title during a triple threat match against Victoria and Stratus in an unsuccessful attempt, to end their feud.
After ending her feud with Stratus, Holly started competing in various singles and tag team matches till the end of 2002 and early 2003, including a second triple threat match for the Women's Championship on the October 28, episode of Raw, ending on both winning and losing sides.
Molly earned her second Women's Championship by defeating Gail Kim on Raw on July 28, 2003. Kim later turned villainous and joined Molly in her feud with Stratus. During an attack on Stratus, Lita made her return, helping Trish fend off her attackers. Holly and Kim then lost a tag team match to Lita and Trish at Unforgiven, sparking a feud with Lita. This feud led to a match against Lita at Survivor Series for the Women's Title, which Holly retained.
Molly lost her championship to Victoria in a four-way elimination match on February 23, 2004. The feud led to a hair versus title match at WrestleMania XX in March 2004, which Molly lost, resulting in her having her head shaved. Over the next few months, in storyline, she desperately tried to disguise her bald head using loose-fitting wigs. Later in 2004, Molly feuded with Stacy Keibler, overpowering Stacy on the mat and pinning her in three consecutive occasions, the last one occurring in a number one contender's match.
Molly Holly's final WWE pay-per-view appearance occurred at Taboo Tuesday in 2004 as she appeared in the Fulfill Your Fantasy Battle Royal along with many other WWE Divas. The fans voted online for the Divas to wear schoolgirl uniforms, as opposed to French maid or nurse outfits. Molly failed to win the match when Stratus eliminated her by tossing her through the ropes for the win. Molly's efforts in subsequent attempts to regain the title failed. Due to several wrestlers from the company's women's division being released in late 2004 and the introduction of the Raw Diva Search program, Molly was mostly left off television, only occasionally appearing on Sunday Night Heat and Raw in losing efforts to the likes of Lita, Victoria, Trish Stratus, and Christy Hemme. Holly left WWE in April 2005.
On December 2007, at the Raw 15th Anniversary, Holly returned during a backstage segment with William Regal, Mickie James and Hornswoggle.
On April 5, 2009, at WrestleMania XXV, Holly returned to compete on the 25-Diva Royal to crown Miss WrestleMania, which was won by Santina Marella.
On January 27, 2016, she appeared on WWE Network's program Table for 3, along with Alundra Blayze and Ivory. She appeared once again on the program, this time along with Candice Michelle and Michelle McCool, which aired on May 18.
On January 28, 2018, at the Royal Rumble, Holly made a surprise entrance at number twelve during the first women's Royal Rumble match, in which she eliminated Sarah Logan before being eliminated by Michelle McCool. On April 6, she inducted Ivory into the WWE Hall of Fame as part of the 2018 class. Molly was also included in the 20-women battle royal at the first ever all-women's pay-per-view, Evolution. She returned, reprising her "Mighty Molly" gimmick at the Royal Rumble on January 26, 2020, entering at number three and being eliminated by Bianca Belair. She also made an appearance on the Raw Legends Night special on January 4, 2021.
On March 10, 2021, it was announced that Molly Holly would be inducted into the WWE Hall of Fame class of 2021. On January 29, 2022, Mighty Molly was a surprise entrant in the Royal Rumble match, but was quickly eliminated by Nikki A.S.H. following a sneak attack during her entrance.