The 46-year-old's decision to step down was announced by chairman Ian Lenagan, following the U's 1-0 victory against Torquay United at the Kassam Stadium on Saturday afternoon.
"My understanding is Chris Wilder has in the last half an hour told the players that he is going and will not be back at Oxford after today," Lenagan is quoted as saying on Sky Sports. "That is all I've heard. I've just looked in his office and he's not there, but it would appear that he has resigned.
"It seems a very peculiar way to do it, but he has told the players. He told me yesterday and the day before that he would resign at the end of the match."
The former Halifax manager's decision to leave comes a day after the club rejected an approach from Northampton Town to speak to Wilder.