Orient skipper Gary Alexander grabbed his 11th league goal of the season to condemn Oxford to only their third league defeat.
Alexander's all-important strike came after 64 minutes when he headed home David Hunt's right-wing corner from six yards.
Oxford stormed back with a late flourish and almost grabbed an injury-time leveller, but young O's keeper Glen Morris made a spectacular save from Andy Crosby's close-range header.
After the game, a delighted Orient boss Martin Ling said: "It was a big win. I thought we played with tempo and purpose in the second half and deserved the points.
"I was happy with our first-half display defensively, although the game was a non-event in the first 45 minutes." Ling was also pleased with his two heroes, skipper Alexander and keeper Morris, adding: "Just recently Gary's scoring record had been A1. It's going well for him at the moment - he is a quality player." He also praised youngster Morris, adding: "He is a quality kid. The save at the end was tremendous but he does that every day in training - ask the players, they hate shooting against him." Oxford boss Ian Atkins said: "I thought the game had nil-nil written all over it - and the only way I could ever see Orient scoring was from a set piece." The win was no more than the home side deserved as they stretched their unbeaten run at Brisbane Road to eight games.
They had two penalty appeals turned down in the first half and Alexander sent an effort just wide, while U's keeper Andy Woodman dived smartly to his right to save Hunt's free-kick on the stroke of half time.
Orient's biggest home crowd of the season, 5433, saw the O's make use of the wind in the second half and Wayne Purser went close to adding a second 12 minutes from time, but was denied by a smart stop from Woodman.