Martin Ling's Leyton Orient took over top spot in League Two in front of their biggest crowd for two seasons.
Oxford, who faced a first-minute setback when Jon Ashton went off with a facial injury, were on the back foot in a first half Orient dominated.
They finally scored on 45 minutes when Craig Easton took advantage of a deflection off Shane Tudor's cross to score with a close-range header.
The Londoners withstood a bold Oxford revival but held out for the points.
Leyton Orient: Garner, Lockwood, Simpson, Mackie, Easton, Keith (McMahon 65), Zakuani, Miller, Tudor, Ibehre, Alexander.
Subs Not Used: Carlisle, Morris, Echanomi, Hanson.
Goals: Easton 45.
Oxford Utd: Turley, Mansell, Robinson, Roget, Willmott, Quinn, Ashton (Stirling 4), Hackett (Hargreaves 45), Davies (Basham 45), Sabin, Bradbury.
Subs Not Used: Tardif, Hughes.
Booked: Mansell, Stirling, Bradbury.
Ref: A Penn (W Midlands).