Sam Deering scored his first senior goal as Oxford started life without Darren Patterson with a fine away win.
The U's, playing under temporary boss Jim Smith, went in front after eight minutes when James Constable headed in after good work from Chris Carruthers.
Nathan Arnold equalised with a superb 25-yard free-kick but Jamie Guy put the visitors back in front on 58 minutes after being played in by Constable.
And substitute Deering's sublime 25-yard effort sealed Oxford's victory.
Mansfield: Gamble, Silk, O'Hare, Moses, Jeannin, Arnold, D'Laryea, Somner, Ahmed (O'Connor 70), Lee (Stallard 80), Sinclair.
Subs Not Used: Kay, Wood, Hurren.
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