A brilliant individual effort by Kemar Roofe on 31 minutes, and Danny Hylton’s 16th goal of the season, in first-half stoppage time, when he headed home a corner, was scant reward for a dominant display in which they completely outplayed Cambridge.
But Hylton missed the target after rounding keeper Will Norris, Alex MacDonald hit a post, Kyle Vassell failed to score when completely through on goal, and Chey Dunkley had a header cleared off the line.
Oxford head coach Appleton said: “We had a lot of good performances from the players.
“I’m a bit disappointed to be honest that we didn’t score a few more goals. We really opened them up with some intricate passing around the box.”
He added: “I didn’t feel we were going to concede today. And going forward we got behind them many times. We could easily have scored six or seven.”
Oxford’s win extended their unbeaten run to seven games, their best run of the campaign.
The victory was slightly marred, though, by a worrying injury to centre half Johnny Mullins, who was stretchered off after 41 minutes after landing badly following an aerial challenge.
Appleton said: “It was a little bit of concussion with him, and we didn’t want to take any risks.
“We’ll need to assess how he is over the next few days.”
Cambridge had little to take from their performance, with only a first-half effort from Sulay Kaikai, which deflected wide, and a long-range shot by Harrison Dunk in the second half, which flashed wide, giving Oxford keeper Jamie Ashdown anything to think about.
Cambridge boss Richard Money showed his displeasure by not spending any time in the dressing room after the game.
But he pointed to the injuries at the club, with defender Greg Taylor having to play.
“He had to, because we didn’t have anyone else,” said Money.
“The best team won. They’ve finished the season better than us. We’ve got one week’s training to go, and one game to go.
“Oxford have finished at home on a high and we have to make sure we do the same next week.”