Vunipola won 79 caps in an England career that began in 2012.
The 32-year-old also made nine Test appearances for the British and Irish Lions.
Saracens forward Vunipola missed last year's World Cup in France because of back surgery, but was expected to be involved in the Six Nations tournament that starts in February.
"It's been an honour to have represented my country but all good things must come to an end," he wrote on Instagram.
"The time has come to step away now. There have been lots of highs and lows. Would love to thank everyone who have helped me along the way.
"To my wife Alex thank you for taking care of our family and all your support. Words don't do it justice.
"To my parents I'm eternally grateful for all you have sacrificed for me to be here. God is good."
Vunipola is currently serving a four-match ban for a dangerous tackle made while playing for Saracens against Newcastle on December 30.
The suspension ends before the Six Nations, which would have made him available for England's first match against Italy on February 3.
With England coach Steve Borthwick facing an injury crisis at loosehead prop, Vunipola was expected to be involved until his surprise decision to step away from the Test arena.
Joe Marler, Ellis Genge and Bevan Rodd, England's three loosehead at the World Cup, are all injured.
Genge could make the trip to Rome, but Rodd misses the entire tournament.
