In Argentina, he is considered one of their best basketball players.
He made his professional basketball debut for the Andino team in the 1995-1996 season and was traded to Bahia Blanca the next year. He played with his hometown team until the Italian league attracted him, and in 1998 he moved to Europe, playing in the 1998-1999 and 1999-2000 seasons with Basket Viola Reggio Calabria, after which he was traded to Virtus Bologna, which he helped take to the championship and to the 2001 Euroleague finals, where he was named MVP. He also made the Italian league's All-Star game three times during this period.
After the 2002 world basketball championships in Indianapolis, (where he won the second place with his national team), he signed with the Spurs, where he is playing in his second season.
Ginobili helped the Spurs climb to the NBA world championship in 2003, when San Antonia beat the New Jersey Nets in six games.