Scunthorpe manager Brian Laws marked his first league game back in charge of the Iron with victory at Walsall.
Niall Canavan nodded in the first from a corner by Mark Duffy, who tapped into an empty net for the second.
David Prutton's straight red card for a challenge on Adam Chambers just before the break offered Walsall hope.
But Canavan powered in another Duffy corner before Leon Clarke's late solo effort, while Will Grigg grabbed a last-minute consolation for the hosts.
For the Iron, it was a welcome contrast from Saturday's heavy FA Cup first round defeat by Gillingham.
Former Wolves striker Clarke's strike was the pick of the goals, latching onto substitute Callum Kennedy's long ball and cleverly lifting it over the advancing keeper David Grof with a neat lob, before slotting home to seal his side's first win in nine games.
Walsall slip three places to 16th after suffering their ninth game without a win.
The highlight of an ineffectual display by Dean Smith's men was a second-half shot by youngster James Baxendale, kept out by a marvellous save by visiting keeper Steve Mildenhall, who also saved Nicky Featherstone's curler.
Grigg did at least get them on the scoresheet after an injury-time blunder by Canavan.
But, up against 10 men for the whole of the second half, the disillusioned home fans who made up Walsall's lowest league crowd of the season clearly expected much more.
VIEW FROM THE DRESSING ROOM
Walsall manager Dean Smith told BBC Sport:
"That's as painful as it's been, standing on the side 4-0 down. We had three experienced players out, in Florent Cuvelier, Andy Taylor and Ben Purkiss, but that's no excuse. We just defended badly.
"And they passed the ball better than us. They've got good players. If they'd played like that two weeks ago, then Alan Knill would still be a job.
"We lost a game here four weeks ago and got clapped off the pitch. Tonight the same group of players got booed off.
"There's two ways you go now. You either sink or you swim. And we'll see how we respond on Saturday."
Scunthorpe manager Brian Laws told BBC Sport:
"It's been a long time coming a result like this, but it's only a small step. There's a lot of games to be played yet and we're not getting carried away.
"We've still got to enjoy this victory though. I walked into our dressing room after and it felt like a grave. I told them to smile and a couple of the players chipped back 'We've forgotten how to'.
"I still live in the town and I was hurting as much as the supporters to see where we are as I thought we were under-achieving.
"But we're delighted with the start we've made. Losing in the FA Cup on Saturday cost us the chance of helping on the financial side, but at least we didn't lose three points. I'd rather have the momentum of winning."