The decision was made a day after the U's lost 3-1 at home to Sheffield Wednesday on Saturday.
"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," a club statement read.
He became the second manager of the weekend to be axed after Gary O'Neil departed Wolves.
Oxford's loss to the Owls extended the club's winless run to a sixth-straight match.
It was also the U's fifth loss in that alarming run of form.
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Buckingham's axing comes just over a year after he was appointed to the role as his predecessor Liam Manning moved to Bristol City.
The 39-year-old guided Oxford back to the Championship for the first time in 25 years thanks to a 2-0 win over Bolton Wanderers in the League One play-off final.
Buckingham's side enjoyed a triumphant return to the second tier with an opening day win over Norwich City.
The U's went on to win two more of their first five games.
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However, Oxford's form quickly nosedived.
The club went on to win just one Championship fixture in their next 15 games, with a 6-2 mauling at the hands of Middlesbrough on November 23 the most damaging of the bunch.
Buckingham also had a minor health scare when he complained of feeling 'dizzy' during the U's 1-1 draw against Derby County in October.
He left the stadium and returned home immediately as assistant coach Craig Short took over post-match media duties.
"He (Buckingham) stayed till the end of the game but two or three times felt dizzy and had to hold on to the side," Short said.
"We asked him whether he'd eaten anything funny but he said no, he'd just had the normal pre-match meal.
"He's been seen by the club doctor and is still not right so we felt it is best if he gets himself away from the stadium and off home."
Oxford had a pre-planned rest day following the Derby fixture as Buckingham returned to take training the following day.
Buckingham departs with Oxford sitting in 20th, two places and one point clear of the relegation zone.
The U's next fixture is a daunting trip to Elland Road for a tricky clash against Leeds on December 21.