McCool first came to World Wrestling Entertainment (WWE) as a competitor in the 2004 WWE Diva Search, losing to Christy Hemme. Although she was eliminated, WWE signed her to a three-year deal in November. She quickly began appearing in backstage segments on SmackDown!, portraying a fitness trainer and teaching various wrestlers stretches. She wrestled in her first SmackDown! match, teaming with The Big Show to defeat Dawn Marie and René Duprée on March 3, 2005. McCool made her singles debut match on March 24, losing to Marie. A few months later, McCool became a part of the feud between MNM (Johnny Nitro and Joey Mercury) and Heidenreich when she defended Heidenreich against MNM's manager Melina's verbal attacks. In a match on June 30, Melina defeated McCool by pinning her with the illegal aid of the ring ropes as leverage.
McCool returned to SmackDown! on June 2, 2006, this time as a heel with a "sexy teacher" gimmick. Upon her arrival, she aligned with Kristal Marshall to feud with Jillian Hall and Ashley Massaro. This feud led to a fatal four-way bra and panties match at The Great American Bash, which Massaro won. She won her first singles match on the July 28 episode of SmackDown!, defeating Hall by illegally using the ropes as leverage.
Soon after, she began acting as valet for the team of K.C. James and Idol Stevens, who, because of her association with them, were nicknamed The Teacher's Pets. The trio began feuding with Paul London and Brian Kendrick, and their valet Massaro, for the WWE Tag Team Championship, but never won the title. The feud ended when London and Kendrick won a match against them at No Mercy in October. On November 28, McCool was hospitalized with an enlarged kidney, a broken sternum, and an electrolyte imbalance. She was released from the hospital on December 2. McCool returned on the March 30, 2007, episode of SmackDown!, where she participated in a 10-Diva tag team match. On the April 13 episode of SmackDown!, McCool became a fan favorite again, when she came to the aid of Ashley after she was attacked by Jillian Hall backstage. Subsequently, a series of matches took place between Victoria and McCool, including a mixed tag team match where Victoria and Kenny Dykstra defeated McCool and Chuck Palumbo.
McCool was then repackaged as "The All-American Diva", where she began accompanying her on-screen friend Chuck Palumbo during matches against Jamie Noble. After a series of matches between the men, Noble won a date with McCool by defeating Palumbo. In the storyline, Palumbo accidentally elbowed McCool during a match, causing her to suffer a concussion. The partnership was dissolved when McCool refused to accept his apology. She then went on to compete in a series of matches with Victoria, Eve Torres, Maryse and Cherry to determine SmackDown!'s top Diva, with McCool winning the title.
On the July 4, 2008, episode of SmackDown!, McCool won a Golden Dreams match to face Natalya for the WWE Divas Championship at The Great American Bash. At the event, on July 20, McCool defeated Natalya to become the inaugural WWE Divas Champion. McCool successfully defended the title against Maryse on SmackDown and at the Unforgiven pay-per-view in September, and against Maria on SmackDown in November. On the December 26 episode of SmackDown!, McCool lost the Divas championship to Maryse. After the match, McCool turned heel by attacking Maria, the special guest referee of the match, and blaming her for the loss. In the following weeks, McCool also attacked Eve Torres, resulting in Torres' debut match, which McCool won.
McCool then defeated Gail Kim on the May 22, 2009, taping of SmackDown to become the number one contender for the WWE Women's Championship. A month later at The Bash, McCool defeated Melina – with help from Alicia Fox – to win her first Women's Championship. With her win, McCool became the first Diva to have won both the WWE Divas and Women's championships. She retained the championship against Melina in a rematch on July 26 at Night of Champions, and also in a Lumberjill match on the October 2 episode of SmackDown!.
McCool then allied with Layla to form LayCool, and the duo entered a controversial feud with Mickie James, in which LayCool bullied James and made fun of her weight. The feud resulted in a five-on-five Survivor Series match at the 2009 Survivor Series, which James' team won, when Melina pinned McCool. James then became the number one contender for McCool's WWE Women's Championship at TLC: Tables, Ladders & Chairs, where McCool successfully retained the championship after interference from Layla. McCool lost the Women's Championship to James at the Royal Rumble, although she regained it on the February 26, 2010, episode of SmackDown! when special guest referee Vickie Guerrero interfered, to become a two-time Women's Champion. On the April 23 episode of SmackDown!, McCool and Layla defeated Beth Phoenix and Mickie James, and attacked Phoenix after the match. This led to McCool losing the championship to Phoenix in an "Extreme Makeover" match at Extreme Rules. On the May 14 episode of SmackDown!, McCool and Layla faced Phoenix in a Women's Championship two-on-one handicap match, in which Layla pinned Phoenix to win the championship. Despite Layla's win, McCool and Layla cut the Women's Championship in half, and the duo were unofficially referred to as the "co-champions".
On the July 30 episode of SmackDown!, McCool took Layla's place in her Women's Championship match against Tiffany, defeating her and retaining the title. At Night of Champions, McCool defeated Melina to unify the WWE Women's Championship with the WWE Divas Championship, becoming the first WWE Unified Divas Champion, and both McCool and Layla carried their own separate championship belts. At Survivor Series on November 21, she lost the Divas Championship when Natalya defeated McCool and Layla in a two-on-one handicap match. At TLC: Tables, Ladders and Chairs, McCool and Layla were defeated in the first Divas tag team tables match by Natalya and Beth Phoenix. LayCool invoked their rematch clause in January 2011, prompting the scheduling of a two-on-one handicap match at the Royal Rumble. At the event, however, the match was altered to a fatal four-way with the addition of Eve Torres, who won the match.
On the April 8 episode of SmackDown!, dissension began to show between McCool and Layla after they were defeated by Beth Phoenix and Kelly Kelly, due to McCool avoiding being tagged in by Layla, citing a back injury. After more arguing and unsuccessful couples therapy sessions in the following weeks, LayCool officially disbanded. On the April 29 episode of SmackDown, McCool faced Layla in a singles match, which ended in a double countout after the two began brawling. After the match, Layla challenged McCool to a no disqualification and no countout match at Extreme Rules. McCool accepted under one condition, which was that the loser leaves WWE. At Extreme Rules, McCool was pinned by Layla, forcing her to leave WWE.
On January 22, 2018, McCool was honored as part of a segment involving women that contributed to the company's success on the WWE Raw 25 Years special episode. The following week as a face, she was a surprise entrant in the inaugural women's Royal Rumble match at the 2018 Royal Rumble, making the most eliminations in the match at five before being eliminated by Natalya. In October, McCool took part in the all women's pay-per-view, WWE Evolution, by participating in a battle royal. She was eliminated from the match by Ember Moon.
On January 29, 2022, McCool returned at the Royal Rumble, entering at number ten and eliminating Dana Brooke. She lasted over twenty minutes and was eliminated by former rival Mickie James. On January 28, 2023, McCool was seen sitting front row for the 2023 Royal Rumble. McCool returned from the crowd at number twenty-five, eliminating Tamina quickly after entering the match and helping ten other superstars eliminate Nia Jax, before being eliminated by Rhea Ripley, making it to the final ten women in the match.