Leyton Orient moved off the bottom of the League One table as they claimed their first away win of the season.
Scunthorpe went ahead through ex-Orient man Andy Barcham, who fired a shot home from the edge of the penalty area.
But Kevin Lisbie scored twice in four minutes, with a calm low finish and a free header, to give the O's the lead.
Scott Cuthbert made it 3-1, heading in Charlie Daniels' free-kick, and the O's held on for the win, despite Barcham bundling in his second after a corner.
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Scunthorpe United manager Alan Knill told BBC Radio Humberside:
"I was disappointed with both halves, but it seems to be just how we are. One minute we play really well, the next we struggle to move the ball around the park and that's pretty much where we were today.
"The pace of the passing and the movement was a little lazy and the first half was a non-event and it was like a practice match."
Leyton Orient boss Russell Slade told BBC London 94.9:
"I'm really pleased. It's a difficult place to come and get a positive result.
"Being one goal down wasn't ideal, but we came back so strongly in the second half, it could have been a lot more.
"We really really believed we could get a result today."