The Chargers released Fluker on Tuesday, parting ways with the offensive lineman they made the 11th overall pick of the 2013 draft.
Fluker was scheduled to make $8.821 million in 2017, the final season of his rookie contract. By releasing him, the Chargers saved the full $8.821 million against their salary cap.
"I'm definitely looking forward to a new start," said Fluker. "Hopefully, I can make a big impact on the offensive line. I think the Giants give me the best opportunity to be successful."
Fluker, who will turn 26 on Monday, started all 16 games at right guard last season. He started all 59 games he played for the Chargers.
Fluker's play has been up and down, but he has missed only five games during his four-year NFL career. After playing his first two seasons at right tackle, the University of Alabama product was moved inside to right guard at the start of the 2015 season, with mixed results.
"D.J. is a young, versatile big man with lots of starts in this league," said Giants general manager Jerry Reese. "He will bring size, toughness and competition to our offensive line unit."
The Chargers' brass liked the energy, enthusiasm and toughness Fluker displayed on game days. However, Fluker struggled at times with speed rushers in pass protection.
Fluker is not a lock for the Giants' starting lineup, as he was ranked 54th out of 72 qualifying guards in Pro Football Focus' rankings this season, with a 63.7 grade. His 46.0 run-blocking grade was among the 11th-lowest among guards.
ESPN's Eric D. Williams and Jordan Raanan contributed to this report.