Wolves, whose 0-0 draw with Brentford on Saturday allowed Orient to move back into top spot, secured the points within the opening 45 minutes, as an error from goalkeeper Owain Fon Williams helped the hosts take the lead through Leigh Griffiths on 23 minutes.
David Edwards added a second three minutes before half time to ensure that the West Midlands outfit capitalised on Orient's 2-2 draw with Bristol City at Ashton Gate to move back to the summit of England's third tier.
Russell Slade's men were twice pegged back in their pursuit of the three points. Sam Baldock cancelled out David Mooney's first-half strike, before Dean Cox saw his 73rd-minute strike negated by an own goal from defender Scott Cuthbert as the Robins earned a valuable point in their fight for survival.
Elsewhere, 10-man Preston North End defied their numerical disadvantage and registered a 2-0 victory away to Port Vale during a feisty affair in Staffordshire.
Joe Garner struck in either half to propel Simon Grayson's men to third in League One, despite being forced to play with 10 men for the majority of the contest.
Neil Kilkenny was given his marching orders on 12 minutes for an off-the-ball incident with midfielder Anthony Griffith, with eight other players booked throughout the course of the game.
The Lilywhites move ahead of Brentford on goal difference, as the Bees scored twice in the final 10 minutes to record a 3-2 victory at home to Peterborough United.
Consequently Darren Ferguson's men sustain a crushing blow in their bid for automatic promotion, with the East Anglians sitting fifth in the standings and 10 points adrift of second-placed Leyton Orient.
Results in full: Bradford City 1-1 Notts County, Brentford 3-2 Peterborough United, Bristol City 2-2 Leyton Orient, Carlisle United 2-1 Crewe Alexandra, Colchester United 3-1 MK Dons, Coventry City 0-3 Rotherham United, Crawley Town 0-0 Swindon Town, Gillingham 3-2 Stevenage, Port Vale 0-2 Preston North End, Sheffield United 1-1 Walsall, Shrewsbury Town 1-2 Oldham Athletic, Wolverhampton Wanderers 2-0 Tranmere Rovers