After winning a gold medal with the Women's Olympic team in the 1996 Summer Olympic Games, Leslie became one of the original members of the Los Angeles Sparks when the WNBA's first season opened in 1997. She had stated her intentions of dunking in a game before the first season even started, and she tried to dunk the ball on the first game of that season, against the New York Liberty, but she missed. She led the WNBA in rebounds in 1997 (9.5 rpg) and 1998 (10.2 rpg).

Throughout the late 1990s, the Sparks kept paving their way to the playoffs, but getting eliminated as the Houston Comets claimed every WNBA championship played in that decade. After winning a gold medal in the 2000 Summer Olympic Games the Sparks were finally able to topple the Comets in 2001, and they beat the Charlotte Sting to win the WNBA title for the first time. In 2001, she was named MVP of the league, the all-star game and the finals, becoming the first player ever to garner all three awards in the same season.

2002 was a very successful year for Leslie. In 2002, she helped win the USA World Championships in women's basketball., and was rewarded with MVP and All-Tournament team honors. On July 22, 2002 she had become the first WNBA player to have over 3,000 career points, when she scored 24 points against the Orlando Miracle.

On July 30, 2002, in a game against the Miami Sol, she became the first woman to score with a dunk in a WNBA game. After a steal by teammate Latasha Byears, Leslie caught Byears's outlet pass and made a fast break, one-handed dunk. The Staples Center crowd and her teammates erupted into a spontaneous celebration that stopped the game for a few minutes.

After winning the MVP Award in the 2002 WNBA All-Star Game, she helped lead the Sparks to their second straight world championship, garnering WNBA Finals MVP honors. She returned to school in the 2002 off-season to work on a Master’s Degree in Business Administration.

On July 29 of 2004, she reached the milestone of 4,000 career points, scoring 17 points in an 85-80, double overtime victory over the Sacramento Monarchs. Later that year she won a gold medal winner with United States women's national basketball team in the 2004 Summer Olympic Games.

At the 2005 WNBA All Star Game, Leslie dunked once again in the closing seconds of the game. It was the both the 2nd dunk of her career in the WNBA as well as the second dunk in the history of the WNBA.

On June 25, 2006, Lisa Leslie scored her 5,000th career point and set an individual career high with 41 points versus the San Antonio Silver Stars. At the end of the season, she was named the WNBA MVP for the third time.