The 34-year-old stroked home the only goal of the game on the 74th minute, though Orient were to see out the final minutes of stoppage time a man light after captain Mathieu Baudry was sent off for a challenge on Kemar Roofe.
After seeing their three-match unbeaten run come to an end last weekend at the hands of Luton Town, player-manager Kevin Nolan made two changes to the starting XI.
Jobi McAnuff and Calaum Jahraldo-Martin came into the side in place of Sammy Moore, who missed out through illness, and Ollie Palmer who dropped to the bench.
There was also a surprise inclusion of defender Shaun Brisley who sported a headband alongside Mathieu Baudry in the centre of defence despite being stretchered off last Saturday.
The trip to the Kassam Stadium was the first time Orient had returned since securing promotion from League Two on the final day of the 2005-06 season, and it was the visitors who appreciated a comfortable start to the game.
Having enjoyed the sharehold of possession early on, striker Jay Simpson had the first opportunity of the game when he sent a header wide of the far post after connecting with Sean Clohessy’s cross from the right.
As the 20-minute mark approached Simpson was then at the heart of another O’s attack as he beat U’s goalkeeper Benjamin Buchel to Jerome Binnom-Williams ball into the box, but Johnny Mullins was on hand to clear with player-manager Kevin Nolan ready to poke home the loose ball.
Despite enjoying a lot of the ball Orient were struggling to create many more opportunities as the half wore on, but with five minutes remaining of the first half came close to edging ahead.
Jobi McAnuff floated a free-kick towards the back post which defender Shaun Brisley knocked back across goal for Nigel Atangana to glance goalwards, only for the Frenchman to be denied his first O’s goal by Mullins on the line.
Kemar Roofe then responded with the first Oxford shot of the half two minutes later, but his shot curled precariously wide of the far post as the sides went into the break goalless.
Following the restart both sides returned for the second half unchanged, and with 49 minutes on the clock Oxford had penalty appeals waved away by referee David Coote following a challenge by Binnom-Williams on Liam Sercombe.
Alex Cisak was then forced into his first save of the afternoon six minutes later, getting down sharply to his left to parry away Roofe’s free-kick from 20-yards, before Nicky Hunt produced a stunning last-ditch challenge to deny Danny Hylton a minute later.
Armand Gnanduillet replaced Jahraldo-Martin on the 63rd minute, and the target man had a wonderful chance to break the deadlock within five minutes of his introduction when played through by Nolan, but the forward could not make the most of the opportunity as Buchel blocked his dinked effort.
With 71 minutes on the clock Orient were then left wondering how they had not taken the lead, when McAnuff spearheaded a counter-attack before releasing Gnanduillet down the left. The striker then beat full-back Jonjoe Kelly before dragging the ball across for Clohessy at the back post, who was denied with two attempts that were bravely cleared off the line by the Oxford defence.
Three minutes later the O’s were to make no mistake however as they broke the deadlock when Clohessy clipped a cross into the box, which deflected off defender Cheyenne Dunkley and into the path of McAnuff who kept his composure to slot the ball beyond Buchel and into the far corner.
U’s substitute George Waring then acrobatically volleyed a shot over the bar as the match entered the final 10 minutes, before Orient made their second substitution as Ollie Palmer replaced Simpson.
The O’s were finding themselves increasingly up against it as the hosts increased their pressure, and Sercombe squandered a chance three minutes from time when he flashed a shot across goal – though the Orient defence were furious the midfielder had not been flagged offside.
With the match in the second of four minutes stoppage time Orient were then dealt a blow as skipper Mathieu Baudry was shown a seemingly harsh straight red for bringing down Roofe on the touchline.
Connor Essam was then thrown on in place of Gnanduillet in a bid to see out the final minutes of stoppage time, and the O’s were able to do just that as they held on for the three points to move up to 7th place in League Two.
OXFORD: Buchel, Kenny, Mullins (C), Dunkley, Skarz, Maguire (O’Dowda 59), Sercombe, Lundstram, Roofe, Hylton (Waring 63), Bowery (MacDonald 81)
SUBS: Slocombe, Ruffels, Ashby, Evans
ORIENT: Cisak, Hunt, Baudry (C), Brisley, Binnom-Williams, Clohessy, Nolan, Atangana, McAnuff, Simpson (Palmer 84), Jahraldo-Martin (Gnanduillet 63 (Essam 90+4)
SUBS: Gregory, Pritchard, Payne, Turgott
GOALS: McAnuff (74)
SENT OFF: Baudry (90+2)
REFEREE: David Coote
ATTENDANCE: 7,102 (788 Orient supporters)