Despite Orient creating a number of chances towards the end of the first half both sides went into the break goalless but substitute Jacob Blyth gave Cambridge a 52nd minute lead with a simple finish.
With 18 minutes remaining Jay Simpson pulled the O’s level however as he calmly rolled the ball beyond Chris Dunn after racing on to Mathieu Baudry’s ball over the top.
On the back of last weekend’s defeat at Exeter, O’s Head Coach Ian Hendon made three changes to the starting line-up.
Alex Cisak returned from international duty to regain his place in goal while Frazer Shaw came in for Alan Dunne at left back.
Jack Payne was also handed his Orient debut as he came in for Dean Cox who dropped to the bench having not trained towards the back end of the week.
In sunny conditions the O’s appeared to start with a flat 4-4-2 formation as Bradley Pritchard and Sammy Moore took up the wide positions in midfield.
Jay Simpson was looking lively during the opening exchanges and the forward was the first to test U’s goalkeeper Chris Dunn on the fifth minute as he latched on to Lloyd James’ quick free-kick to fire straight at the stopper although the flag was raised for offside.
Cambridge were winning several corners early on and Alex Cisak then had his blushes spared on the 19th minute as Josh Coulson nipped in to beat the O’s goalkeeper to Luke Berry’s corner but could only glance his effort wide.
With chances few and far between Jack Payne had the opportunity to mark his debut with a goal when the ball dropped to him 20 yards out but despite his shot being on target it was well blocked by Mark Roberts.
Moments later Simpson really should have broke the deadlock as he used his pace to race onto a ball over the top of the defence but failed to bring the ball into his stride at the first attempt before crashing and effort off the post from a tight angle.
The O’s were certainly growing into the tie and Connor Essam was next to trouble the host’s goal as he met James’ corner at the near post with a powerful header that Dunn superbly tipped over the bar.
Mickey Demetriou responded with a chance for Cambridge instantly however as he lashed a volley into the roof of the stand, before Jordan Slew wasted a wonderful chance as he could only head Luke Berry’s cross wide of the post.
Pritchard combined well with Simpson inside the Cambridge half but the former could only direct a powerful shot wide from outside the penalty area after working some space.
With half-time looming the O’s then created a number of chances as they looked to make the breakthrough.
Firstly, Pritchard closed down a clearance from Leon Legge that looped over the head of Dunn in the U’s goal but the goalkeeper was able to get back to his line and push the ball over for a corner.
Sammy Moore was then denied by an excellent low save from Dunn at the near post having been touched through by Pritchard as the O’s continued to push forward.
Paul McCallum then saw a powerful header parried away to force a third consecutive corner before directing another effort wide as the half ended goalless despite the late series of chances.
During the interval Cambridge made two changes as Liam Hughes and Jacob Blyth came on and it was the latter who made an immediate impact with the opening goal on the 52nd minute.
A ball in behind Clohessy saw Demetriou collect the ball near the corner flag and as the O’s defence failed to react Blyth was left unmarked to slot the low cross beyond Cisak.
Demetriou was causing Orient numerous problems down the left and with the match just shy of the hour mark another cross from the full-back was met by Robbie Simpson who sent a shot into the side netting.
With 25 minutes remaining Blair Turgott replaced James to give the O’s some much needed width, but it was to be a more direct approach that pulled Ian Hendon’s side level seven minutes later.
Simpson’s pace was proving too much for the Cambridge defence to handle and a ball over the top from Mathieu Baudry saw the striker race in behind before keeping his composure to fire in the O’s equaliser.
Having grabbed the equaliser Orient pushed forward for a winner throughout the closing stages but it was not to be forthcoming as the Cambridge defence remained resolute as they prevented the visitors from creating any clear cut chances.
The O's could well have grabbed all three points deep into added time when Moore took aim from distance but his impressive shot was pushed over well by Dunn as both sides were forced to settle for a point.
CAMBRIDGE: Dunn, Omozusi, Legge, Roberts (C), Coulson, Demetriou, Newton, Berry, Carr (Hughes HT), R Simpson, Slew (Blyth HT)
SUBS: Beasant, Morrissey, Taft, Akintunde
GOALS: Blyth (52)
BOOKED: Robertson (10), Blyth (56), R Simpson (83)
ORIENT: Cisak, Clohessy, Baudry (C), Essam, Shaw, Pritchard, James (Turgott 65), Payne, Moore, McCallum (Palmer 77), J Simpson
SUBS: Grainger, Dunne, Maguire, Cox, Kashket
GOALS: J Simpson (72)
Referee: Oliver Langford
Attendance: 5,821 (1,739 Orient fans)