After three seasons playing at Seton Hall for head coach Mike Sheppard, DeFrancesco was selected in the ninth round of the 1984 draft by the Boston Red Sox. During a nine-year minor league playing career, DeFrancesco played in 567 games and advanced as high as AAA, but never played in the majors.
Manager
Minor League manager
After retiring as a player, DeFrancesco began his managing career in 1994 with the Arizona League Athletics. In 2003 Tony DeFrancesco moved up to the Pacific Coast League's Sacramento River Cats, where he led the team to a 92-52 record in his first year, earning him the 2003 Minor League Manager of the Year from The Sporting News. DeFrancesco would continue to lead the River Cats to PCL championships in 2004 and 2007. In 2008, DeFrancesco became the third base coach for the Oakland Athletics. In 2009, Oakland announced that DeFrancesco would return to the Sacramento River Cats as manager, replacing Todd Steverson. On November 30, 2010, the Athletics announced that Darren Bush would replace DeFrancesco as manager of the River Cats.
Houston Astros
On August 19, 2012, the Astros announced DeFrancesco would be the interim manager of the major league team for the remainder of the 2012 season, replacing Brad Mills. He won his first game in his fifth game as manager when the Astros defeated the New York Mets on August 24. With his appointment late in the 2012 season, DeFrancesco served as the final manager of the Astros as a National League franchise. He finished with a record of 16 wins and 25 losses. The Astros were in the midst of a major rebuild at the time, and on the way to their second consecutive 100-loss season; DeFrancesco's.390 winning percentage was actually a significant upgrade over the.322 win percentage the 2012 team had achieved before DeFrancesco's tenure.
Return to the minors
He was the manager of the Triple-A Fresno Grizzlies from 2015 to 2017. During his first season, he led the Central Valley team to become the Triple-A champions. It was the team's first time winning the Triple-A championship in 18 seasons. Tony DeFrancesco then won Baseball America Minor League Manager of the Year Award. DeFrancesco was named manager of the AAA Las Vegas 51s of the New York Mets organization for the 2018 season. He stayed as the Mets moved their AAA team to upstate New York, remaining manager of the 2019 Syracuse Mets in their inaugural season. He was interviewed as a possible candidate to become the next Mets manager in their search during the 2019 offseason. The job ultimately went to Carlos Beltrán.
New York Mets
On December 8, 2019, DeFrancesco was named the first base coach for the New York Mets.
