Prior to turning professional, DeFazio attended Clarkson University where he played four seasons of NCAA Division I men's ice hockey with the Clarkson Golden Knights men's ice hockey team. After graduating from his senior year with Clarkson, DeFazio joined the Pittsburgh Penguins affiliate teams, the Wheeling Nailers of the ECHL and the Wilkes-Barre/Scranton Penguins to end the 2010–11 season.
DeFazio was signed by Wilkes-Barre to a one-year AHL contract, and was also given a try-out and attended Pittsburgh's NHL training camp for the 2011–12 season.
On July 2, 2012, DeFazio signed as a free agent to a one-year, two way contract with the New York Islanders. A year later, though, DeFazio left the Islanders organization as a free agent and signed a one-year contract with the Vancouver Canucks on July 12, 2013.
In the 2014–15 season, DeFazio received his first NHL recall by the Canucks on November 9, 2014. He made his long-awaited NHL debut that night in a 2-1 shootout victory over the Anaheim Ducks. DeFazio played in his second career game on November 11 against the Ottawa Senators, where he collected the first shot of his career while playing 5 minutes and 49 seconds.
On July 6, 2015, having left the Canucks as a free agent, DeFazio returned to the Eastern Conference in signing a one-year, two-way contract with the Boston Bruins.
In the off-season, DeFazio left the Bruins organization as a free agent an on July 25, 2016, he was signed to a one-year contract to continue in the AHL with the Texas Stars. In the 2016–17 season, DeFazio compiled a career best 47 points in appearing in every regular season game with Texas.
After 6 seasons largely in the AHL, DeFazio as a free agent agreed to a one-year deal with Chinese club, HC Kunlun Red Star of the KHL on June 6, 2017.
His father, Dean De Fazio, also played professional hockey within the Penguins organization. DeFazio's was recognized for his work in the community, earning his AHL team's man of the year award multiple times.