Jon Stead's goal wasn't enough for Notts County as a brace from Sammy Moore and a solitary strike by Jay Simpson gave Leyton Orient a 3-1 win at the Matchroom Stadium.
Moore had opened the scoring with a volley from 12 yards before Stead equalised at the start of the second half with a low drive from a narrow angle.
However, Notts couldn't hold on for a point on the road as Simpson made the most of a loose ball in the area to give the initiative back to the home side.
Then Moore scored a spectacular third for the O's to seal the points and send the Magpies home empty-handed.
Ricardo Moniz made nine changes to the team with all seven substitutes from Tuesday's draw at Dagenham - Scott Loach, Civard Sprockel, Gill Swerts, Curtis Thompson, Julian Jenner, Jack Barmby and Stead - all named in the team. Thierry Audel and Jimmy Spencer also came into the side whilst Alan Sheehan and Alan Smith were the only players to retain their place in the starting line-up.
That meant Roy Carroll, Mike Edwards, Elliott Hewitt, Liam Noble, Graham Burke, Adam Campbell, Izale McLeod all dropped to the bench.
Notts started the game on the front foot and missed an early chance within two minutes as Sprockel headed wide from Jenner's corner.
At the other end, Loach did well to turn away Moore's volley from close-range after being found by a deep cross from Sean Clohessy. Home captain Mathieu Baudry headed wide from the resulting corner after outjumping Sprockel.
Another Baudry header caused danger from a set-piece but Loach was equal to the effort, leaping spectacularly to his left to claw the ball away from danger.
Orient's pressure told and they got the opening goal just after a quarter of an hour when Moore volleyed past Loach after springing the offside trap to get on the end of Bradley Pritchard's lofted ball over the top of the defence.
Dean Cox tried his luck unsuccessfully from 25 yards, dragging a shot well wide of goal before the hosts missed a glorious chance to double their lead when Swerts' misdirected header went straight to Simpson, who put his own header straight at Loach.
County tried to get back on level terms, though Jenner's sliced effort from 12 yards ended up getting stuck on the roof of the stand at the Matchroom Stadium.
Sprockel did well to block Simpson's effort on the turn whilst Cox saw a shot cannon clear off a Notts defender.
Thompson found some rare space in midfield and advanced 40 yards before shooting wide via a deflection as Moniz's side started to look more lively going forward.
Neat footwork from Spencer on the left side of the penalty area opened up a chance for a cross, but no Notts player was there to take advantage and the opportunity went begging.
Moniz tweaked his line-up shortly before half-time with Campbell coming on in place of Sheehan, meaning Barmby moved to left-back.
Jenner curled into the advertising hoardings from just outside the penalty area as Notts went into the break a goal behind.
McLeod came on for Spencer at half-time, leaving Moniz with one final substitution in the second half to turn the game around.
The manager would, no doubt, have asked for a quick response from his team during the interval and he certainly got it with the Magpies equalising within a minute of the restart.
Clever play by Smith set substitute Campbell scampering away and the former Newcastle man picked out Stead at the end of his run, who slammed in at the near post for his first league goal in County colours.
Jenner scuffed an effort wide and Stead's shot was blocked by Orient's central defender Connor Essam as the momentum shifted in Notts' favour.
Notts were clearly in the ascendancy and almost took the lead when Stead's low cross was hit first time by Campbell, who was denied his second goal of the week by a superb save by the legs of goalkeeper Alex Cisak.
Ollie Palmer headed over from a long diagonal ball for the hosts and Smith threw himself in the way of a Cox shot to take the sting out of the effort.
A mishit clearance by Audel led to another chance for Orient, but fortunately Blair Turgott got his angles wrong at the back post and skewed his shot off-target.
Moniz made his final roll of the dice by bringing on Hewitt for Jenner with Barmby moving back to the wing.
Loach smothered a grass-cutter by Palmer but it wasn't long before the O's were celebrating again.
Turgott's reverse pass played Clohessy in and Loach could only parry the full-back's shot to the six-yard box, where Simpson pounced to rifle into an empty net and restore the lead for Ian Hendon's team.
The home side made sure of the three points when Moore picked the ball up 35 yards out and unleashed an unstoppable swerving effort which sailed into the top corner, giving Loach no chance.
The game ended as it had begun, with Sprockel heading over from a corner as Notts' away-day woes continued.
Notts: Loach; Swerts, Audel, Sprockel, Sheehan (Campbell, 42); Jenner (Hewitt, 73), Smith, Thompson, Barmby; Stead, Spencer (McLeod, 45).
Subs not used: Carroll, Edwards, Noble, Burke.
Attendance: 5,193 (377 away)