Garcia played college football at Gavilan College, coached by his father, and San Jose State University, and started his professional career as a backup to Doug Flutie with the Calgary Stampeders of the Canadian Football League. After Flutie was traded to the Toronto Argonauts, Garcia took over as starting quarterback. He led the Calgary Stampeders to a Grey Cup championship in November 1998, a game in which he was named the MVP.

Following the Grey Cup victory, Garcia signed with the San Francisco 49ers of the National Football League. He set the 49ers' team record with 4278 passing yards in the 2000 season, although the team finished with a 6-10 record. Garcia led the 49ers to the playoffs in both the 2001 and 2002 seasons. He was named to the Pro Bowl three consecutive seasons. During the 2002 playoffs, he was a large reason why the 49ers defeated the NY Giants in the second largest comeback victory in NFL playoff history.

On January 14, 2004, Garcia was arrested for a drunk driving violation in San Jose, after attending a San Jose Sharks game, by the San Jose State University Police Department.

Following the 2003 season, Garcia was released by the 49ers due to salary cap issues, and signed a contract with the Cleveland Browns on March 9, 2004.

In the summer of 2004, Garcia was forced to fend off allegations of homosexuality made by a former 49ers teammate, wide receiver Terrell Owens, in an interview Owens gave for Playboy magazine. At the time, Garcia was dating 2004 Playmate of the Year, Carmella DeCesare.

He was released by the Browns after the 2004 season. He was signed by the Detroit Lions to a one-year contract on March 12, 2005, but broke his leg (fibula) in the fourth preseason game against the Buffalo Bills on September 2, 2005. He started his first regular season game as quarterback for the Lions on October 23, 2005 against the Cleveland Browns. Garcia led the Lions to a 13-10 victory completing 22 of his 34 pass attempts for 210 yards, zero touchdowns and zero interceptions. Shortly after the game coach Steve Mariucci declared that if Garcia remained healthy that he would remain the starting quarterback, replacing Joey Harrington, who had started 37 consecutive games for Detroit. However, Garcia struggled later in the season, possibly due to his injuries, which led to Harrington returning as the starter.

On March 15, 2006, Garcia signed a one-year deal with the Eagles, where he will serve as the backup to Donovan McNabb.

Jeff Garcia is one of only six quarterbacks in NFL history that have achieved two consecutive (back-to-back) 30-touchdown passing seasons at least one time in their careers. The others are Steve Bartkowski, Brett Favre, Dan Fouts, Dan Marino and Y.A. Tittle.