Palmer, appointed in midweek after four months as caretaker boss, was booed off the pitch by disgruntled home fans for the second successive Saturday as Oxford marched to only their second win in six games.
The visitors' pace on the break destroyed a nervous Mansfield and, after being gifted an early breakthrough, Oxford then sealed victory through two Chris Hackett goals.
Palmer had made five changes, including giving a full debut to on-loan Birmingham striker Andrew Barrowman and bringing back long-term absentees Scott McNiven and Rhys Day after four-month injury lay-offs.
McNiven, who has won his fight with testicular cancer, was also made captain, but it was Oxford who went on to dominate from the kick-off.
After Lee Bradbury had gone close in the opening minutes Oxford finally took the lead in the eighth minute after two errors by the ring-rusty Day.
First his poor clearance went straight to Bradbury and, when the striker nodded the ball back into the area, a static Day allowed Steve Basham to shoot unchallenged into the roof of the net.
The Stags rarely looked like equalising in a scrappy opening half hour, with Adam Rundle blazing over and Adam Murray testing the keeper from long range.
In the 33rd minute Oxford doubled their lead. After narrowly failing to spring the offside trap on many occasions Matt Robinson finally succeeded and Hackett raced clear on to his pass to lob the advancing keeper.
Six minutes into the second half Oxford secured victory. Mansfield's substitute Fraser McLachlan inadvertently flicked on a long Chris Tardif goal kick and Hackett raced clear again to roll the ball past the stranded keeper.
Mansfield went close to a consolation when Barrowman volleyed over from an acute angle, McLachlan was twice off target and then Gareth Jelleyman's low drive was well held by the keeper.
But in the final minute the home side at last grabbed a goal. Substitute Simon Brown was tripped in the area by Jon Ashton and fellow substitute Colin Larkin netted from the twice taken penalty.