Kenny Jackett's table toppers are six points ahead of second-placed Brentford, who sealed the second automatic promotion spot with a 1-0 win over Preston North End on Good Friday.
But with just three games left to play, and taking into account Wolves' vastly superior goal difference, even a Brentford victory at MK Dons on Monday is unlikely to be enough to keep Mark Warburton's slim hopes of the title alive.
At the bottom, Stevenage are seven points adrift of safety and defeat at home to mid-table Bristol City would confirm their relegation, while Carlisle United visit Peterborough United for a match that could hold huge significance at both ends of the table.
Darren Ferguson's Peterborough will look to bounce back from their 1-0 loss at Bradford City to re-assert their play-off credentials, while their conquerors on Friday could have a further say on whether the Football League Trophy winners finish in the top six.
Bradford travel to seventh-placed Swindon Town and a win for the visitors would see Peterborough secure sixth with victory over Carlisle.
Defeat would be another body blow for Graham Kavanagh's team, who are fourth bottom and two points from safety after Walsall's Michael Ngoo netted late on to secure a 1-1 draw last time out.
The three teams immediately above Carlisle - Colchester United, Tranmere Rovers and Crewe Alexandra - are locked together on 46 points having played a game more.
That situation will change as Crewe and Colchester face off at Gresty Road after the sides experienced contrasting fortunes against fellow strugglers last time out.
Mathias Pogba, Uche Ikpeazu and Anthony Grant were on target as Crewe saw off second-bottom Shrewsbury Town 3-1, while Colchester lost 1-0 at home to Oldham Athletic courtesy of a Connor Brown strike.
Tranmere host Sheffield United, whose game in hand means they retain faint play-off hopes - as do Port Vale ahead of their trip to Rotherham United.
Like Orient and Preston, Rotherham are already preparing for the play-offs and came out on the wrong side of a remarkable 6-4 scoreline at Wolves on Friday.
Shrewsbury will hope Preston's minds are already on other things as they head to Deepdale five points from safety with three games remaining.
One place above them, Notts County entertain Crawley Town having lost 2-1 at Bristol City on Friday.
At Boundary Park, 16th plays 17th and a winner in the match between Oldham and Coventry City would take a significant step towards safety, while Walsall host Gillingham.
