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John Egan’s goal was enough to send Gillingham through to the area final of the Johnstone’s Paint Trophy.
Egan headed the Gills infront late in the second half, from a corner, scoring his third goal in two games.
The Gills will meet either Bristol City or Coventry City in a two-legged southern area final.
Gills boss Peter Taylor left his two leading scorers out of the starting XI for the match. Cody McDonald had one of the five places on the bench but Danny Kedwell didn’t feature.
Luke Norris, who missed out last week through illness, returned to spearhead Gills’ attack as they looked to make it past the area semi-final stage of the Football Trophy for the first time.
Orient, with former Gills players Romain Vincelot and Josh Wright in midfield, had the better of the first half chances but they were unable to get past keeper Stuart Nelson.
The Gills stopper held onto a deflected Shane Lowry free-kick, watched another one dip over the bar and did well to tip over Gianvito Plasmati’s close-range header.
Norris looked odds-on to put the Gills ahead with a chance midway through the half, after Leon Legge nodded a Jake Hessenthaler free-kick into his path, only for Lowry to make a goal-saving block.
Brennan Dickenson, who was partnering Norris upfront, almost got through on goal himself, after O’s keeper Adam Legzdins hit a clearance against him. But a slight tug from Legzdins went unnoticed by the referee and allowed the visitors to clear.
Dickenson was presented with an early second half chance, when Legzdins lost the ball on the edge of the box, but the Gills striker was unable to capitalise.
Norris came close just before the hour mark, volleying an Egan cross just wide of the post from the corner of the area.
Bradley Pritchard put a great chance wide for Orient with 20 minutes left and Scott Cuthbert headed a corner just past Nelson’s post moments later.
Egan – who netted twice the week before against Port Vale - headed the Gills infront from a Michael Doughty corner with 11 minutes left. It was Gillingham’s first effort on target.
Pritchard missed a golden opportunity to level on 86 minutes, with the goal empty, but couldn’t get his head to a left-sided cross.
Bristol City and Coventry meet in their area semi-final on Wednesday night.
Gillingham: Nelson, Hessenthaler, Chicksen, Egan, Ehmer, Legge, Doughty, Dack, Loft (McGlashan 73mins), Dickenson, Norris (McDonald 73mins). Subs: G Morris, Pritchard, Hoyte.
Leyton Orient: Legzdins, Omuzusi, Sawyer, Vincelot, Cuthbert, McAnuff (Cox 80mins), Lowry, Wright, Pritchard (Kashket 89mins), Mooney, Plasmati (Batt 73mins). Subs: Baudry, Grainger.
Attendance: 3,103 (620 away)