In June 2000, Team Xtreme began a storyline with T & A (Test and Albert), with Lita engaging in a rivalry with their manager, Trish Stratus. The rivalry developed into an off and on long-term feud between the two women that lasted until Stratus retired in 2006. The storyline ended shortly after Fully Loaded, where Lita pinned Stratus in a six person intergender tag team match. Subsequently, Lita began feuding with WWF Women's Champion Stephanie McMahon-Helmsley. In the main event of the August 21, 2000 episode of RAW is WAR, Lita defeated Stephanie with a moonsault to win the Women's Championship for the first time. The match also featured The Rock as the Special Guest Referee and constant interference from Triple H and Kurt Angle.
Lita held the Women's Championship for seventy-three days, which included retaining her title in a hardcore match against Jacqueline on October 9. In the course of her reign, Lita became embroiled in the storyline feud between the Hardy Boyz and Edge and Christian. In retaliation for her frequent interference in their matches, Edge and Christian cost Lita the Women's Championship, helping Ivory defeat her in a four way match on the November 2 episode of SmackDown. Ivory was in a conservative-based stable named Right to Censor at that time, which targeted Lita for her attire and moves. Lita attempted to regain the title on several occasions, wrestling Ivory at Survivor Series and Rebellion, but she was thwarted on each occasion by Steven Richards, Ivory's mentor. She spent the remainder of the year in a storyline with Dean Malenko, on one occasion unsuccessfully challenging him for the WWF Light Heavyweight Championship.
Lita continued to feud with Dean Malenko in early 2001, and she defeated him in a singles bout on the February 19 episode of Raw is War with the assistance of Matt Hardy. Following the match, Hardy kissed Lita, beginning their on-screen relationship and turning their real-life romance into a storyline. The couple wrestled in several intergender tag team matches throughout the early part of the year.
In July 2001, Lita and Trish Stratus joined forces to combat Stacy Keibler and Torrie Wilson, members of The Alliance. At the Invasion pay-per-view on July 22, Lita and Stratus defeated Keibler and Wilson in the first ever tag team bra and panties match by stripping their opponents to their underwear. Throughout The Invasion, Lita, Stratus, and Jacqueline feuded with Alliance members Keibler, Wilson, Ivory, and Mighty Molly. The Invasion storyline ended on November 18 at Survivor Series, where Lita took part in a six pack challenge for the WWF Women's Championship, which had been vacated by Chyna earlier that month; Stratus won the match and the title.
In late 2001, the Hardy Boyz began a storyline in which they were feuding with one another. Lita refereed a match between them at Vengeance on December 9. Jeff won the match with a scripted finish that had Lita failing to notice that Matt had placed his leg on the rope during Jeff's successful pin attempt. Continuing the storyline on the following episode of Raw, Matt defeated Lita and Jeff in a handicap match, shortly after informing Lita that both their relationship and the Hardy Boyz were finished. On the December 17 episode of Raw, both Jeff and Lita were sidelined with storyline injuries following a title match between Jeff and WWF Hardcore Champion The Undertaker. The injuring of both his brother and ex-girlfriend led to a reconciliation between the members of Team Xtreme, and on the December 20 episode of SmackDown!, Matt faced The Undertaker but was also injured. All three members of Team Xtreme were then removed from WWF television for several weeks.
The Hardy Boyz, along with Lita, returned to WWF television in February 2002. Lita resumed her pursuit of the WWF Women's Championship in March 2002 and made her in-ring WrestleMania debut at WrestleMania X8 on March 17, facing Stratus and WWF Women's Champion Jazz in a match in which Jazz retained her title by pinning Lita.
She began making appearances on Sunday Night HEAT as a color commentator, beginning in October 2002. On the April 21, 2003 episode of Raw, as part of a new storyline, she was fired from her position as Sunday Night HEAT color commentator by General Manager Eric Bischoff after she rejected his advances and his request that she follow in the footsteps of SmackDown!'s Torrie Wilson and pose for Playboy.
She returned to the ring after an absence of seventeen months on the September 15 episode of Raw, saving Trish Stratus from a beating at the hands of Molly Holly and Gail Kim. Co-General Manager Stone Cold Steve Austin later explained to Eric Bischoff that he had rehired Lita. Lita and Stratus went on to defeat Holly and Kim in a tag team match on September 21 at Unforgiven. Lita feuded with Holly into late 2003, unsuccessfully challenging her for the Women's Championship on November 16 at Survivor Series. On the November 17 episode of Raw, Lita and Matt Hardy were reunited after Hardy was moved from SmackDown! to Raw. Continuing the storyline, Holly interrupted as Hardy was about to propose to Lita, challenging the duo to face her and Bischoff in an intergender tag team match later that evening. Bischoff later added the stipulation that Lita would earn a title shot if she won but would be fired if she lost. Hardy and Lita lost the match after Hardy refused to tag in, with Hardy berating Lita for "selfishly" returning to Raw instead of SmackDown!, claiming that this showed that she cared more about the Women's Championship than about him. Lita was rehired later that evening when Christian informed her that he had used his Survivor Series favor to get Bischoff to reinstate her. One week later, Lita lost to Victoria in the first ever women's steel cage match in WWE history, due to interference from Hardy.
As Lita and Christian appeared to be developing an on-screen relationship, so did Stratus and Chris Jericho. Subsequently, Stratus and Lita participated in an intergender tag team match as partners on the December 1 edition of Raw. After the match, Stratus overheard Jericho talking to then-heel, Christian, about who could sleep with their respective woman first. One week later, Stratus and Lita confronted the men about their actions, leading to a feud between the two men and women which resulted in a "Battle of the Sexes" match at Armageddon, which the women lost. A rematch the next night ended in a no contest.
Lita competed in the Women's division throughout early 2004, winning a battle royal to become the number one contender for the Women's Championship on the April 5 episode of Raw. Victoria defeated Lita to retain the Women's Championship at Backlash on April 18. The next night on Raw, Lita was reunited with Matt Hardy when Hardy attacked Kane in an attempt to prevent him from harming Lita, beginning a new storyline involving the trio. In the following weeks, Kane began repeatedly assaulting Hardy and attempting to seduce Lita. During the course of the storyline, he kidnapped Lita and held her tied up backstage, and he persuaded Eric Bischoff to give her a title shot at Bad Blood on June 13, where she was defeated by the evil Trish Stratus in a Fatal Four Way match that also included Gail Kim and entering champion Victoria. The next night on Raw, Lita revealed that she was pregnant. One week later, it appeared that Hardy was going to propose to Lita, but he was interrupted by Kane, who claimed to be the father of Lita's child. Two months later, it was revealed that Kane was, in fact, the father. Hardy and Kane feuded for several months, culminating in a "Till Death Do Us Part" match on August 15 at SummerSlam, with the stipulation that Lita would be obliged to marry the winner of the match. Kane won the match, leading to he and a reluctant Lita marrying one another on the August 23, 2004 episode of Raw. Despite being married to Kane, Lita thwarted him during his matches, constantly aiding his opponents. On the September 13 episode of Raw, Lita miscarried after Gene Snitsky struck Kane with a chair, resulting in him falling on Lita. The miscarriage led to Lita and Kane joining forces in order to take revenge on Snitsky.
With the pregnancy storyline over, Lita returned to the women's division in November 2004. She began a feud with Trish Stratus after Stratus called Lita "chubby" because of her pregnancy weight gain. Lita challenged Stratus to a Women's Championship match at Survivor Series, however, due to the months of humiliation and being verbally berated by Stratus, Lita was more concerned with doing as much damage as possible, leading to her disqualification. The feud continued, and on December 6, Lita was booked to defeat Stratus in the main event of Raw to win her second WWE Women's Championship. During the course of the match, Lita botched a suicide dive to the outside when she over rotated by a fraction, barely escaping serious injury. This move was later used in the build up to the title rematch she was booked for at New Year's Revolution against Stratus, who claimed, "Lita had to practically kill herself, just to beat me". She defeated Lita, ending her second reign as Women's Champion on January 9, 2005 at New Year's Revolution. In the course of the match, Lita tore her left ACL after executing a Thesz press off the ring apron.
Lita returned to WWE television in March 2005, mentoring Christy Hemme, who was in the midst of a storyline with Stratus that featured a title match between them at WrestleMania 21. Despite Lita's coaching, Hemme was defeated by Stratus. Lita continued to feud with Stratus by proxy over the following weeks, with Kane defeating Stratus' companion, Viscera, at Backlash on May 1.
The relationship between Lita and Kane lasted until the May 16 episode of Raw, when Lita took on a villainous role by betraying Kane, helping Edge defeat him in the finals of the Raw Gold Rush Tournament. On the May 30 episode of Raw, Lita announced that she had filed for divorce, and said things such as Kane was like a 4th grader in the bedroom, that she would not have to deal with things such as his sweaty body, the "stupid little" laugh he does, and the wedding ring being flushed down a toilet. She then attempted to marry Edge on the June 20 episode of Raw, but the marriage ceremony was interrupted by a vengeful Kane, who emerged from beneath the ring, destroyed the ceremony, and as Edge and Lita escaped from the ring, Kane tombstoned their priest. The storyline with Kane ended shortly thereafter.
In April, Matt Hardy was released from WWE, only to be rehired several months later. Lita continued to act as Edge's valet, and Edge defeated Hardy at SummerSlam. On the October 3 episode of Raw, Edge, with the assistance of Lita, defeated Hardy in a ladder match, and Hardy was obligated to leave Raw as a stipulation of the match. Edge defeated John Cena to win the WWE Championship on January 8 at New Year's Revolution. On the February 6 episode of Raw, Lita teamed with Edge in a loss to Cena and Maria. She continued to manage Edge into mid-2006, frequently interfering on his behalf during his feud with Mick Foley. In May 2006, Foley joined forces with Edge and Lita, with the trio defeating Foley's ECW rivals Terry Funk, Tommy Dreamer, and Beulah McGillicutty in an impromptu six person tag team match at One Night Stand after Edge speared and pinned Beulah. On the August 14 episode of Raw, Lita won her third Women's Championship by defeating Mickie James. She lost the title to longtime rival, Trish Stratus, at Unforgiven in Stratus's retirement match. The next night on Raw, the Women's Championship was vacated and a tournament was scheduled to determine a new champion. Lita won the tournament at Cyber Sunday defeating Mickie James. With her 4th championship reign, Lita announced that her final match would be at Survivor Series. Lita lost her final match and the title to rival, Mickie James.
She made a special appearance on December 10, 2007 on Raw's 15th Anniversary Special by teaming up with former long-time rival/real-life friend Trish Stratus to rid the ring of Jillian Hall, and afterwards celebrated in the ring with Stratus, turning face in the process, and later that night, she had a backstage reunion with Kane, her former on-screen husband. She also appeared on the November 1, 2010 episode of Raw in a backstage segment with Pee Wee Herman. On December 12, 2011, Lita appeared as the Slammy Award presenter for the "Divalicious Moment of 2011" on Raw, which was presented to Kelly Kelly.
She also appeared at WWE Wrestlemania Axxess, and later was seen sitting front row with CM Punk at the WWE Hall of Fame 2012, leading to her attendance for Wrestlemania 28. Lita returned on the 1000th episode of Raw defeating Heath Slater in a no disqualification, no countout match with the help from the legends who had defeated Slater during the past weeks as well as the APA. She also made an appearance at the 2013 WWE Hall Of Fame with CM Punk.
On the February 10, 2014 edition of Raw, WWE announced that Lita will be inducted into the WWE Hall of Fame the night before WrestleMania XXX.