Callum Kennedy’s stunner of a free-kick had put the O’s in front, but were pegged back on the stroke of half time by Jordan Houghton.
Mandeville then sent Orient goalkeeper Alex Cisak the wrong way from two spot kicks as the Yorkshire hosts remained unbeaten at home.
Edwards made three changes from the side which lost 1-0 at home to Exeter City on Tuesday, with Nicky Hunt missing out through an ankle injury, Gavin Massey suspended and Paul McCallum dropped to the bench. In came Aron PollocK, Sandro Semedo and Ollie Palmer.
Chances were few and far between in the eary stages as both sides settled into the contest, though the hosts had more of the possession.
Doncaster won a few corners, but failed to test Alex Cisak in the O’s goal until on the quarter of an hour mark when he superbly tipped over former O’s loanee John Marquis’ header following a Rovers set piece.
From the corner Orient were in more trouble when Tommy Rowe met the delivery and his effort thundered against the bar and the O’s were able to clear the danger.
The O’s hadn’t created a clear cut opportunity but when Jay Simpson was pulled back 30 yards from goal and referee Rob Jones awarded a free-kick.
Up stepped Callum Kennedy and his fantastic curling effort nestled into the corner with home goalkeeper Marko Marosi unable to keep it out despite being at full stretch.
Rovers went straight up the other end though and were close to levelling almost immediately only for Jordan Houghton’s fierce strike deflected behind for another corner.
Liam Mandeville, scorer of the hosts’ winner in the 2-1 win over Hartlepool United in midweek, went closer still though as he received the ball just outside the box and his curling effort had Cisak at full stretch, however, the strike struck the bar to the O’s relief.
Coppinger then saw a shot deflected behind for a corner with 33 minutes on the clock as the hosts continued to put Orient under pressure.
Two minutes of stoppage time had just been announced and with that the O’s conceded as the ball fell kindly to Houghton just outside the box and his low drilled effort find a way into the bottom corner.
There was still time for the hosts to create further opportunities and Coppinger went agonisingly wide of the goal with Cisak at full stretch once more, but the half was to end 1-1.
No changes were made at the break by either side but the hosts carried on where they left off as Mandeville saw an effort deflected into the side netting then Coppinger drilled an effort across goal and wide.
Josh Koroma was brought on with 12 minutes of the second half played for Sandro Semedo, but his first impact was to fell Matty Blair in the box and referee Jones awarded a spot kick.
Mandeville stepped up to take the spot kick and sent Cisak the wrong way to give the hosts the lead.
Paul McCallum was brought on as a like-for-like substitute for Palmer but within a minute of coming on the hosts had another penalty when Tommy Rowe’s mazy run across the pitch ended with Parkes bringing him down in the box.
Mandeville remained on spot-kick duty, and this time went the other way but still found the net to open up a two-goal cushion for the hosts.
McCallum had an impact off the bench though and after some fine play from Koroma and Kennedy the striker forced Marosi into a top save, before Koroma fired over a minute later.
Orient kept battling to the end, with plenty of encouragement on the sidelines from Edwards and assistant manager Danny Webb, but the O’swere unable to find a late second which could have caused an anxious finale for Darren Ferguson’s side.
Doncaster Rovers: Marosi, Mason, Butler, Alcock, Baudry, Houghton, Blair, Rowe, Coppinger (c) (Beestin 90), Marquis, Mandeville (Longbottom 90+3).
Subs: Jones, Wright, Evina, Keegan, Calder.
Goals: Houghton (45+1), Mandeville (59 pen, 66 pen)
Orient: Cisak, Kennedy, Parkes, Pollock, Judd, Semedo (Koroma 57), Weir (c), Atangana, Collins, Palmer (McCallum 65), Simpson.
Subs: Sargeant, Dunne, Bowery, Dalby, Janse.
Goals: Kennedy (20)
Booked: Atangana (38)
Attendance: 5,135 (366 Leyton Orient fans)
Referee Rob Jones.