The 29-year-old sustained the injury in the first quarter of his side's win over the Buffalo Bills on Sunday on his first running attempt of the match.
"We're going to put him on IR [and] he'll be done for the year," head coach Mike McCoy told reporters. "He broke his fibula, so it's unfortunate. He means a lot to our organisation.
"His love for the game, the way he plays, his love for his teammates, the way he practises; he's a great guy to be around.
"One of the first guys in the building, he only knows how to do it one way. He starts his day off early [at] five in the morning and is a true professional. So we're going to miss him."
Woodhead recorded 72 total yards from scrimmage for the Chargers this season.