"I would like to take this opportunity to announce my retirement from international rugby," he said in a statement on his website.
"To do so fills me with great sadness but I know that I have been blessed in so many ways to have experienced what I have with the England rugby team."
Wilkinson, 32, enjoyed a highly successful international career spanning 13 years and 91 caps.
His drop goal in extra time secured England's victory over Australia in the 2003 World Cup final in Sydney and he helped his country reach the final again four years later when they lost to South Africa.
"I never ever believed that I would be able to give up on this dream which has driven me to live, breathe, love and embrace the game of rugby from the earliest days that I can remember," Wilkinson added.
