Lee Steele, returning to his former club for the first time, scored after just 12 seconds for the fastest goal in Orient's history.
It came straight from the kick-off when Oxford defender Leo Roget tried to chest the ball back to goalkeeper Chris Tardif but made a mess of it and Steele nipped in to score from a tight angle.
However, Oxford were level after 17 minutes when Steve Basham scored a goal out of nothing. His left-foot shot from 20 yards beat Glen Morris and nestled in the bottom corner.
Chris Hackett provided most of the home side's attacking threat with raids down the right and some quality free-kicks and corners.
Tommy Mooney almost gave Oxford the lead before half time when he out-jumped Justin Miller at the far post only to see his downward header flash a yard wide.
Basham then volleyed over the bar from 14 yards from Mooney's chipped cross.
It was Mooney who put Oxford in front nine minutes into the second half with a low angled volley from Barry Quinn's cross.
Moments earlier, Oxford felt they should have had a penalty when Orient defender Gaby Zakauni handled.
But 19 minutes from the end, Michael Simpson diverted home a Gary Alexander shot from 20 yards to make it 2-2 to finally end Oxford's already slim play-off hopes.
Indeed Alexander nearly snatched victory for an Orient side which included six scholars in their squad when he headed against the post two minutes from the end.