United striker David Kitson hit a goal in each half and Lloyd Opara added to Cheltenham’s misery with a late third.
Bobby Gould named the same side that had earned a creditable 0-0 draw with league leaders Oxford United on Tuesday and the Robins started in a confident mood.
Following a bright opening, Cheltenham lost Mike Duff, who hobbled off to be replaced by his younger brother Shane.
Cambridge took the lead after a good move culminated in John Turner supplying an inch-perfect cross for Kitson to head past Shane Higgs in the Cheltenham goal.
Turner, 17, was making his first start for the U’s, coming in to the line-up in place of the injured Daniel Chillingworth and the young striker also played a part in his side’s second after an hour.
Turner’s long ball over the top caught the home defence square and Kitson held off the challenge of Shane Duff before firing a powerful shot past Higgs.
Devaney crashed a shot into the side netting and forced a good save from Shaun Marshall, while Lee Howells was not far off with two long-range efforts.
The Cambridge defence held firm and Cheltenham were frustrated in their efforts to haul themselves back into the game.
Opara added the third after 87 minutes, beating Higgs with a low shot after good work on the right from Luke Gutteridge to leave Gould’s men without a win in three third division games.