The U’s extended a tricky run of form to just one win in 15 games after slipping to a 3-1 defeat at home against Sheffield Wednesday.
The loss left United 20th in Sky Bet Championship, in what is their first season back in the second tier for 25 years.
The news comes as a huge surprise and will no doubt send shockwaves across the club and the fanbase, with Buckingham guiding the U’s to promotion via the play-offs last season.
United said in a statement: “Oxford United can confirm that Des Buckingham has left his role as men’s first team head coach.
“Des was appointed in November 2023 and led the club to promotion to Sky Bet Championship at the end of the 2023/24 season.
“The club would like to place on record its thanks to Des for everything he has done during his time with us and wish him well for the future.
“The appointment of a new head coach will be confirmed in due course.”
More to follow.