Peter Leven's penalty after 16 minutes gave Chris Wilder's team a third straight league win after Tom Craddock had his heels clipped by Sido Jombati as he raced into the penalty area.
Former Leeds and Chelsea centre-half Michael Duberry made his first start of the season following neck surgery last summer, and he and Jake Wright gave little away.
Oxford posed most of the attacking threat with Sean Rigg causing Cheltenham a lot of problems down the left.
Alfie Potter saw a 20-yard drive beaten out by 'keeper Scott Brown while both Rigg and Duberry failed to make good enough contact when presented with good opportunities in a crowded box.
Cheltenham's scoring chances were few and far between. Jermaine McGlashan broke free down the left and cut inside but his side-footed shot was comfortably saved, while in the second half Russell Penn's 30-yard drive went straight into the chest of 'keeper Ryan Clarke.
Substitute Shaun Harrad injected more urgency into the Robins and he went close with a sharp turn and drive that flew over the bar.
In stoppage time Jombati headed a free-kick just over as Town came up short at the Kassam Stadium.
