Safin was born in Moscow, USSR (now Russia), to an ethnic Tatar, Muslim family and is a non-practising Muslim. His parents were former tennis players and coaches. His younger sister is a professional tennis player Dinara Safina. Safin's father managed the local Spartak Tennis Club where Safin trained in his youth alongside several tennis players, including Anna Kournikova Elena Dementieva and Anastasia Myskina. At age fourteen he moved to Valencia, Spain, to gain access to advanced tennis training programs which were not available in Russia. Safin says he grew up "very fast...with no muscles" and that he moved to Spain because clay courts were "better for the knees." Safin speaks fluent Spanish as a result.

Safin held the No. 1 ATP ranking for 9 weeks during 2000 when he won his first Grand Slam tournament at the US Open, by defeating Pete Sampras in straight sets. Sampras praised him as "the tennis of the future." However, a succession of injuries hindered his progress and Safin missed the majority of the season in 2003 as a result. Safin reached the final round in three more Grand Slam tournaments, all in the Australian Open in 2002, 2004, and 2005. He has cited nervousness as the reason for his loss in the 2002 event, and physical exhaustion for the 2004 loss.He defeated home-country favorite Lleyton Hewittin the 2005 finals to secure his second Grand Slam in five years. En route to this final, he defeated top-ranked Roger Federerin a five-set semi-final match. After ending Federer's 26-match winning streak over top-10 players, Safin described the match as "a brain fight." His best result at the Wimbledon is reaching the quarterfinals in 2001, often losing in the first or second rounds. In 2002, he reached the semifinals of the French Open, his best performance there to date.

Safin is known for his emotional outbursts during matches, and has smashed numerous rackets. Safin is estimated to have smashed 48 racquets in 1999. He frequently verbally berates himself for lost points, speaking in the languages of Russian, Spanish and English. He is also known for having arguments with the chair umpires.