Laila, who is a personal trainer in Los Angeles, surprised the boxing world in 1999, by announcing she would try a hand at women's boxing.

To much fanfare, she made her debut on October 8 of that year, knocking out April Fowler in the first round. She rallied off 8 wins in a row, and many among boxing's fans started talking about wanting to see her and George Foreman's daughter, Freeda Foreman, or Joe Frazier's daughter, Jackie Frazier-Lyde square off in a boxing ring. On the evening of June 8, 2001, Ali and Frazier finally met, in a fight that became the first time a women's boxing fight was the main event of a Pay Per View event in history, a fight which was also nicknamed Ali/Frazier IV in allusion to their fathers' famous fight trilogy, and fight which was part of the International Boxing Hall Of Fame induction weekend's activities.

Ali won by an eight-round majority decision, and then took off almost one year, returning 364 days later, to beat Shirvelle Williams by a six-round decision. She won the IBA title with a two-round knockout of Suzzette Taylor, on August 17 at Las Vegas, and on November 9, she retained that title and added the WIBA and IWBF belts, by unifying the crown with an eight-round knockout win over her division's other world champion, Valerie Mahfood in Las Vegas, Nevada.

On June 21, 2003, Ali retained the title in a rematch with Mahfood, knocking her out in six rounds. It was announced, on June 30, that she would fight Christy Martin on August 23. She beat Martin by a knockout in four rounds.

Laila Ali would have begun 2004 by fighting Gwendolyn O'Neil of Guyana, at Abuja, Nigeria. The fight was cancelled, however, when Ali's camp learned no airline had flights scheduled to Nigeria on the date she wanted to arrive there.

On July 17 of that year, she retained her world title, knocking out Nikki Eplion after four rounds. Ali dropped Eplion four times before the fight was stopped.

Thirteen days later, she stopped Monica Nunez in nine rounds, as part of the undercard where Mike Tyson was surprisingly knocked out by journeyman Danny Williams, at her father's native city of Louisville, Kentucky.

On September 24, 2004, she added the IWBF Light Heavyweight title to her resume by beating O'Neal, the fighter against whom she had had to cancel a fight previously, by a knockout in three rounds, at Atlanta, Georgia.

Returning to Atlanta on February 11, 2005, Laila Ali scored a commanding and decisive eighth round technical knockout over Cassandra Geigger, in a scheduled 10-round fight.

On June 11, 2005, as the undercard in the Tyson-Kevin McBride fight, Laila Ali pounded Erin Toughill into submission in round three to remain undefeated, and became the second woman to win a World Boxing Council title (Jackie Nava was the first), in addition to defending her WIBA crown. Erin was outclassed in 1:59 of the third round. Toughill, her face bleeding profusely, took approximately 20 consecutive punches in her corner, before referee Joseph Cooper stepped in to end the fight.

On December 17, 2005, in Berlin, Germany, Laila fought and defeated Sandell by TKO in the fifth round, marking her 22nd win.

Ali's record stands at 22 wins and 0 losses, with 19 wins by knockout.