Tommy Mooney grabbed his first goal in eight games to give Oxford boss Graham Rix a massive boost.
The U's had lost six in a row and Graham Rix's job was on the line, but Oxford chairman Firoz Kassam came down to the touchline at the final whistle to shake his hand and show he still had his backing.
Tommy Mooney powered home a right-wing cross from David Mackay just before half-time to bring Oxford their first victory since September 25.
And Oxford had done it with a completely new system as Rix changed from a 3-5-2 with a new signing Sam Togwell coming in as one of three centre halves.
Oxford played the ball around crisply, showing few signs of any lack of confidence despite their poor form.
Lee Bradbury went close when he cut inside and hit a fierce shot which was well saved at his near post by Shane Higgs.
And in the second half, Lee Bradbury missed a golden chance to put the game out of Cheltenham's reach.
He was put clear by Tommy Mooney's header but got his feet in a mess and tripped over the ball.
John Melligan drove into the side netting as the Robins pressed hard for an equaliser.
Nervous Oxford keeper Simon Cox came to his sides rescue in the closing stages.
First he saved a cross shot from sub Damian Spencer, and in the final minute he scrambled across goal to save a goalbound header from Jamie Victory.
It was Cheltenham's first defeat in seven matches and they have failed to score a goal now in three visits to the Kassam Stadium.
Boss John Ward tried everything, bringing on all three subs in the second half,but Oxford's defence kept them out.
When the impressive Grant McCann spread play to his right, Steve Guinan had a great chance to level at the end, but his low shot went right to Cox.