Vunipola, who plays for Saracens, has made 79 appearances for England, winning three Six Nations championships, and he played in the 2019 World Cup final alongside his younger brother Billy.
"It's been an honour to have represented my country but all good things must come to an end," Vunipola said in an Instagram post. "The time has come to step away now."
Vunipola suffered a back injury last season and did not recover in time to earn selection for the 2023 World Cup. He is currently serving a four-match suspension at Saracens.
"There have been lots of highs and lows," Vunipola added.
"Would love to thank everyone who have helped me along the way."
His retirement will add to England's problems at loosehead prop ahead of the Six Nations, with Joe Marler, Ellis Genge, Bevan Rodd and Val Rapava-Ruskin all sidelined due to injuries.