He made his first division debut on 21 September 1991, against Nancy. He joined Olympique Marseille and won the European Cup at the end of his first season in 1992.
On 26 May 1994, he won his first cap for France against Australia. He won the World Cup with France, conceding two goals in seven games in his home country in 1998. He won a European Championship with France in 2000. He played in France's World Cup again in 2002. However, France was knocked out in the first round.
In 1995, Barthez joined AS Monaco and won the French title in 1997 and 2000. He joined Manchester United for 7.8 million pounds in 2000. He won League Championships title with Man U in 2001 and 2003.
In October 2003, Man U agreed that Barthez would join Olympique Marseille on loan. However, FIFA blocked the loan deal on the grounds that it was not agreed upon within the international transfer window. The two clubs agreed on a loan deal after the next transfer window opened on 1 January 2004, and Barthez joined Olympique Marseille soon afterwards.