John Brebbia grew raised in Sharon, Massachusetts, and finished his junior year at Sharon High School. In order to better his prospects of receiving a collegiate baseball scholarship, he switched to Wellington High School in Wellington, Florida for his senior year.
He had a 10–1 win–loss record with a 0.83 earned run average (ERA) and an 18-strikeout game as a senior at Wellington. Brebbia attended Elon University in Elon, North Carolina, after graduating from Wellington, where he pitched for the Elon Phoenix baseball team.
Brebbia helped the Phoenix earn an at-large bid to the 2009 NCAA Division I Baseball Tournament during his rookie year. In 27 bullpen appearances during his junior year, he was 7–1 with a 1.76 ERA.
Brebbia signed a one-year, $800,000 contract with the San Francisco Giants on December 21, 2020. Brebbia was put on the 60-day disabled list on February 17, 2021, while he recovered from Tommy John surgery.
On June 20, he was activated off the disabled list, having recovered from Tommy John surgery in less than the usual 13-15 months.
Brebbia pitched for the Giants in the regular season in 2021, going 0-1 with a 5.89 ERA. Over the course of 18 games, he pitched 18.1 innings. He was 3-0 with a 2.93 ERA in 17 games (2 starts) for AAA Sacramento, pitching 15.1 innings.
Brebbia avoided salary arbitration by signing a $838,000 contract with the Giants on November 30, 2022.