Wrexham displaced Gateshead at the top of the Blue Square Bet Premier table with a dominant and composed display.
Danny Wright gave the depleted visitors a perfect start with a fourth-minute curler from inside the area.
Joe Clarke, making his first start, made it two early after the break with a deflected strike and Mark Creighton headed a third 10 minutes later.
Gateshead captain Kris Gate replied almost immediately, but a Dean Keates penalty wrapped up victory for Wrexham.
Substitute Johnny Hunt saw his effort cleared off the line as the visitors ended the match in complete control, giving caretaker manager Andy Morrell his third win in four games since taking the helm.
Gateshead, meanwhile, were left to contemplate their first home defeat of the season.
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Wrexham caretaker manager Andy Morrell told BBC Radio Wales:
"To get an early goal made them come out and they had to play. They did have a lot of possession, but only shots from outside the box until the goal.
"I'm delighted for the lads. We were down the the bare bones as well and the lads that came in are a credit to themselves.
"All the lads that haven't played a lot of games recently have stood up and been counted."