Mansfield picked up their fourth win in a row as they swept aside Cambridge, who could only name four substitutes.
James Jennings' stunning free-kick from 20 yards flew into the net via the post to put the hosts ahead.
Ross Dyer pegged them back almost immediately when he headed home Luke O'Neill's delivery, while Andy Pugh's overhead kick whistled over for United.
But the U's defence then failed to clear their lines and were punished when Louis Briscoe blasted home.
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Cambridge United manager Jez George told BBC Radio Cambridgeshire:
"We looked what we are - a really patched up team and against a side like Mansfield it makes it really difficult because they're such a powerful, physically strong team. We've just got to dig in and we know the situation.
"It's a really tough moment for us. I look back earlier in the season and there's me getting frustrated when we played poorly and won.
"I'd take them now and I'll never be disappointed with a win again."
Mansfield Town manager Paul Cox told BBC Radio Nottingham:
"I'm delighted with the lads because, more than anything, they looked a bit jaded mentally and physically.
"So to come here against a very good side and not just get a point but all three is excellent.
"What we're tending to be doing now is grinding out results. I don't think we played particularly well tonight but we've ground out a result against a good side."