Cheick Diabate’s last gasp winner was all to separate the two sides, with City pushing their bid for a spot in the play-offs.
The 20 year-old's towering header sent the home crowd into raptures with a 93rd minute winner following an Archie Collins pin-point free kick delivery.
Despite a couple of chances for both teams, the first half failed to separate the two teams with the most significant chance falling to Orient striker Aaron Drinnan.
The second followed a similar story, with neither side capitalising on the few chances on offer, until the stoppage time winner.
With the home crowd now in full voice, City held on for another win and a fourth clean sheet in five league matches.
In a similar line-up to City’s dramatic late victory at Swindon, Matt Taylor made one change with Jack Sparkes coming into the fold for Jake Caprice.
Taking advantage of the calmer conditions compared to the weekend, The Grecians made an urgent start with deadline day signing Kieran Phillips finding himself through on goal thanks to a ball from skipper Matt Jay, but Lawrence Vigouroux was able to get down low to make a good save to his left.
On the 14th minute presented their way to City with a few chances to trouble The O’s back line, notably with Jevani Brown looking to drop his shoulder to break through on the right.
The vocal crowd support for The Grecians encouraged the starting 11, with Phillips being presented with a near post diving header from the left.
Immediately following this, the best chance of the half came from a quick Leyton Orient break which allowed Aaron Drinan through on goal from the halfway line, thankfully for City the striker was unable to convert a great opportunity.
5 minutes before half time, some intricate play down the left-hand side involving Jevani Brown and Archie Collins led to the number 8 with a promising volley on the edge of the box, but unable to keep the shot on target.
There was a significant break at the start of the second half following an unfortunate injury for Orient defender Daniel Happe, with Shadrach Ogie coming on to replace him.
The 55th minute allowed Sam Nombe to make his second appearance off the bench since his injury lay-off, replacing club captain Matt Jay.
10 minutes later saw some good combination play between Key and Sweeney, with the Irishman threading a ball low across goal, but Vigouroux was able to collect after initially spilling the cross.
The following stages of play presented little opportunities for either team, but the Exeter faithful continued in their support for the Grecians.
Josh Key was an ever present down the right wing for City in the second half, winning a few corners which the red and white forwards were unable to convert into the back of the net.
It was difficult to separate both sides towards the end with Exeter having the majority of the chances as well as possession. A few speculative chances from Archie Collins and defender Sam Stubbs failed to find the target, firing very much off target.
A couple of efforts in the last 10 minutes from Leyton Orient threatened to trouble the home defence, but The O’s failing to find the target from a header in the centre of the box.
Looking to capitalise on the 6 minutes of added time, The Grecians found themselves with a free kick on the edge of the box. Midfielder Archie Collins delivered a sumptuous ball over the top of the Orient defence, with academy graduate Cheick Diabate heading in from the middle of the box for his first goal at SJP in the closing minutes.
Exeter City: Dawson, Stubbs, Diabate, Sweeney, Sparkes, Key, Collins, Dieng (82’), Jay (55’), Brown, Phillips (67’)
Subs: Brown, Taylor (82’), Grounds, Coley, Atangana, Amond (67’), Nombe (55’)
Leyton Orient: Vigouroux, Happe (50’), Thompson, Beckles, Mitchell, Kyprianou, Khan, Pratley, Young (67’), Drinan, Nouble (93’)
Subs: Byrne, Ogie (50’), Moss, Reilly (67’), Sotiriou (93’), Fish
Referee: Carl Brook
Attendance: 4,111 (192 away)