Mauresmo was not yet four when she watched countryman Yannick Noah win the French Open, and his victory inspired her to take up the game. She took to tennis easily, and in 1996 she was ranked the number one junior player in the world. She won the junior French Open and Wimbledon titles during that campaign and was named junior world champion by the International Tennis Federation.

Moving up to the Women's Tennis Associaton (WTA) Tour, Mauresmo swiftly made her mark. After finishing 1998 ranked number 29 in the world, in 1999 she reached her first grand slam final at the Australian Open and climbed to a number 10 ranking. She made off-the-court headlines that year by publicly coming out as a lesbian, becoming the first prominent female tennis player to do so since Martina Navratilova (Navratilova, Martina) in 1981. Mauresmo slipped to number 16 in 2000 but returned to the top 10 the following year. She concluded the 2002–04 seasons among the top four in the world (briefly residing at number one in September 2004), and she led France to victory in the 2003 Fed Cup, winning all eight of her singles matches.

Despite reaching at least the quarterfinals in 12 of the 14 grand slam tournaments that she played during 2002–05, Mauresmo faltered frequently in the key stages of tight contests, often succumbing to nerves. A crucial turning point in her career occurred in 2005. At the singles final of the WTA Tour championships—an illustrious event featuring only the top eight players in the game—she defeated her compatriot Mary Pierce. Her success on that important occasion carried Mauresmo confidently into 2006 as she displayed a new level of match-playing maturity and poise under pressure. She won the first grand slam event of the year, the Australian Open, when Justine Henin (Henin, Justine) withdrew from the final because of a stomach ailment while Mauresmo led 6–1, 2–0. Mauresmo again beat Henin in the Wimbledon final, becoming the first Frenchwoman in 81 years to win the event. Although Mauresmo failed to reach the semifinals at the French and U.S. opens, she spent most of 2006 ranked as the number one player in the world. While her level of play slipped slightly the following season, Mauresmo remained a fixture at the top of the WTA rankings, finishing 18th in the world at the end of the 2007 season. In addition to her on-court success, she was named a knight of the French Legion of Honour in 2007.