It was recently announced that the 25-year-old would not be signing a new contract at St James' Park, where he had risen through the ranks to make 263 appearances.
"It's exciting to be joining Oxford. I have been with Exeter since I was a kid so it was hard to leave but I know I have made the right decision," he told the club's official website.
"I wanted a new challenge and am really looking forward to being part of what Oxford are trying to build here."
Sercombe scored 23 goals in all competitions for the Grecians.