In 1996, she captured both the Junior French Open and Wimbledon titles; she was named 1996 Junior World Champion by the International Tennis Federation.

In 1999, the then unseeded Mauresmo reached the Australian Open final with wins over three seeds (including world No. 1 Lindsay Davenport), before falling to No. 2 Martina Hingis; she was only the second Frenchwoman to reach the Australian Open final dating back to 1922 (Mary Pierce won it in 1995) and third Frenchwoman to reach any Grand Slam final in the Open Era. She lost in the final to Hingis but later in the year, soundly defeated her en route to the final of the Paris [Indoors] event.

It was after her surprise upset of Davenport at the semi-finals of the Australian Open that Mauresmo came out as a lesbian to the international press. Unlike the comings-out of players like Billie Jean King and Martina Navratilova, Mauresmo experienced neither public fallout nor loss of any lucrative commercial endorsements from her sponsors; she received tremendous support from the French public, and sports companies Nike and Dunlop continue to sponsor and use her in many of their commercials.

In 2003, Mauresmo captured the Fed Cup for France. She has won more Fed Cup singles matches than any other French player.

Mauresmo captured a silver medal at the 2004 Olympic Games in Athens, where she was defeated by Belgian Justine Henin-Hardenne in the women's singles final.

On September 13 2004 she became the first French tennis player to become number one since computer rankings began in the 1970s.

At the 2005 WTA Tour Championships she claimed the title, rebounding from a first-set loss to defeat countrywoman Mary Pierce (5-7, 7-6, 6-4) in a rematch of their Round Robin encounter, which Pierce won in three sets. This is the most remarking victory of her career. In round-robin play she defeated Elena Dementieva (6-2 and 6-3) and #2 seedKim Clijsters (6-3 and 7-6), suffering her only loss at the hands of Mary Pierce (6-2, 4-6 and 2-6). By finishing in second place in the Black Group behind Pierce, she earned a spot in the semifinals where she outclassed Russian Maria Sharapova (7-6, 6-3) with beautiful points.

She is one of the few players to reach the top spot without first winning a Grand Slam event; other notable players who did so were Belgian Kim Clijsters, who ascended to the top spot in 2003, two years before winning her first Grand Slam title at the US Open, and Ivan Lendl, who first reached number 1 in 1983, before winning any of his eight Grand Slam titles. She is considered the best player on the tour not yet to have claimed a Grand Slam title.