Lockwood, Orient's record penalty scorer, coolly converted the 75th minute spot-kick to send the Stags to only their second defeat in 12 games and clinch Orient's first away win in four attempts.
Jake Buxton clumsily brought down Donny Barnard as the ball broke loose in the penalty area to give Lockwood the chance to stretch the Londoners' fine run to just one defeat in 12 games.
Deep into injury time the home side almost grabbed a point to keep their promotion hopes alive, but substitute Alan Russell, who had snatched a last gasp leveller a week earlier at Lincoln - curled wide of an empty net from 20 yards.
The home side were almost given the perfect start when Jonathon D'Lareya hooked wide from an Adam Rundle short corner.
At the other end they were fortunate to survive when a Michael Simpson cross evaded everyone before keeper Kevin Pressman gratefully smothered the ball.
Orient wing man Wayne Corden, on his return to the club where he enjoyed several successful seasons, then curled wide before Joe Keith's long range drive was well held by the diving keeper.
As the action swung back to the other end, Richard Baker skied high and wide on the end of Rundle's 25th minute cross.
The club's leading scorer then headed Rundle's deep 37th minute free-kick past the post as he searched for his 23rd goal of the season.
A vital block from veteran defender Jon Olav Hjelde denied Simpson a 52nd minute breakthrough as Orient started the second half on top.
As the pressure mounted Gary Alexander just failed to convert a Paul Connor cross.
But against the run of play Mansfield should have taken the lead.
Barker charged down a Simpson clearance on the halfway line and raced clear on goal. But with just keeper Glyn Garner to beat and substitute Simon Brown well placed the striker lifted his final 12-yard shot over the bar - and just two minutes later Orient snatched their vital winner.