In his youth, Duncan excelled in freestyle swimming and had hopes of participating in the Olympics after seeing his older sister, Tricia, compete as a member of the Virgin Islands swim team in 1988. The following year, however, Hurrican Hugo destroyed most of the island's swimming pools, and Duncan was left unable to train. He began playing basketball and proved a natural at the sport, but he attracted little interest from college scouts. In 1993 Duncan entered Wake Forest University, Winston-Salem, N.C., where he gained national attention with his all-around play and poise. He was predicted to be the number one pick in the NBA draft following his junior year, but Duncan elected to stay in school. In his final season he received the John R. Wooden Award as the outstanding collegiate player in the United States.

After graduating with honours in 1997, Duncan was the Spurs' first overall pick. He and teammate David Robinson formed the dominating tandem known as the “Twin Towers,” and in 1998 Duncan was named Rookie of the Year. The following season he averaged 24 points and 17 rebounds in the NBA Finals against the New York Knicks to give the Spurs the franchise's first NBA title and earn himself the finals Most Valuable Player award. In 2000 he was named co-MVP of the All-Star Game, but he later suffered a knee injury that ended his season and forced him to withdraw from the U.S. men's Olympic basketball team.

After recovering from his injury, Duncan's performance in the 2001–02 season—in which he became the 14th NBA player to have registered more than 2,000 points and 1,000 rebounds in a single season—secured him the league's MVP award. In 2003 he led the Spurs to victory over the New Jersey Nets, scoring a triple double (21 points, 20 rebounds, and 10 assists) in the decisive sixth game to claim the NBA title and his second finals MVP award. He was also named MVP for his regular-season play. In 2004 Duncan finally realized his dream of competing in the Olympics, helping the U.S. men's basketball team win a bronze medal at the Athens Games.

Off the court, Duncan was involved in charitable works. In 2001 he created the Tim Duncan Foundation, which, among other things, worked to raise funds for youth sports and recreation in San Antonio, Winston-Salem, and the U.S. Virgin Islands.