A lacklustre first-half showing from the hosts saw Oxford race into a two goal lead through goals from Kemar Roofe and John Lundstram, before a double substitution at half-time by Ian Hendon triggered a much-improved display after the break.
Jay Simpson then pulled a goal back on the 65th minute with his tenth of the season before the visitors were reduced to 10-men when Jordan Graham was given his marching orders two minutes later.
With time running out substitute Scott Kashket then equalised in stoppage time with his first senior goal to snatch a dramatic point.
It was the first time these sides has met since the dramatic final day of the 2005-06 season, and for the clash Orient Head Coach Ian Hendon made three changes.
Mathieu Baudry returned in defence to captain the side, while Blair Turgott and John Marquis also came into the side as the O’s lined up with a flat 4-4-2 formation.
Blair Turgott was making his first League start of the season and the winger had the opportunity to cap it with a goal inside the opening two minutes when Dean Cox pulled the ball back for him inside the penalty area, but he was unable to get a shot away under pressure.
Oxford came into the tie full of confidence having recorded victories in each of their previous fixtures and it was the visitors who took a 16th minute lead.
Having only manage to half-clear an Oxford corner, Jordan Graham then delivered a curling ball into the box which Mathieu Baudry could only touch into the path of Kemar Roofe who gleefully swept home from six-yards.
The O’s were struggling to grab a foothold of the tie and as the half wore on started to appear frustrated at the lack of opportunities created.
Those frustrations were to then grow as the visitors doubled their advantage with 12 minutes of the first half to play when former Orient loanee John Lundstram’s strike from distance took a wicked deflection off Connor Essam to wrong foot Alex Cisak and drop over the O’s goalkeeper who was already diving down to his right.
In need of a strong response the hosts created a half chance just before the interval when a Cox cross was eventually scrambled behind for a corner which Baudry could only head down into the ground before it bounced over the crossbar.
Changes were needed during the break and O’s Head Coach opted to make a double substitution, bringing on Jack Payne and Ollie Palmer for Cox and Turgott as they reverted back to the familiar diamond formation which saw Marquis drop behind the strikers.
Despite seeing a lot of possession after the break the hosts had little to show during the early minutes as Baudry headed over from a free-kick in what was the only chance.
With 25 minutes left to play the O’s were then handed a lifeline as they pulled a goal back through Simpson as he rifled home a knockdown from Palmer following a delightful lofted pass from Payne.
The goal was Simpson’s tenth of the season and a minute later Marquis nearly snatched an equaliser as he got up well to meet a Clohessy cross but his header was parried behind by U’s goalkeeper Sam Slocombe.
The goal had sparked Orient into life and a minute later the match appeared to swing even more in their favour when the visitors were reduced to 10-men as referee Ross Joyce showed a second yellow card to Graham for kicking the ball away.
Scott Kashket was then introduced as the final O’s change on the 79th minute but moments later Oxford’s Liam Sercombe had two chances to put the game to bed.
The midfielder was first denied by a strong save from Cisak when through one-on-one, before seeing a volley from the edge of the area wonderfully touched round the post.
As four minutes of injury-time was raised, up stepped Kashket to save the day.
A ball into the Oxford penalty area was only cleared as far as the youngster on the edge of the box who made no mistake by drilling home his first goal for the Club with a low right-footed shot into the bottom far corner.
In added time the O's then had chances to grab a late winner through Simpson, but the forward could only fire over as both sides settled for a share of the spoils.
ORIENT: Cisak, Clohessy, Baudry (C), Essam, Chicksen, Turgott (Payne HT), Pritchard, Moore, Cox (Palmer HT), Marquis (Kashket 79), Simpson
SUBS: Grainger, Shaw, James, Moncur
GOALS: Simpson (65), Kashket (90+1)
BOOKINGS: Cox (23)
OXFORD: Slocombe, Baldock, Mullins, Wright (C), Skarz, Sercombe, Lundstram, Graham, O’Dowda (MacDonald 80), Roofe, Taylor (Hoban 80)
SUBS: Büchel, Rose, Hylton, Ruffels, Dunkley
GOALS: Roofe (16), Lundstram (33)
BOOKINGS: Graham (54 & 67), Slocombe (68), Taylor (76), Sercombe (90+5)
SENT OFF: Graham (67)
REFEREE: Ross Joyce
ATTENDANCE: 6,296 (1,388)