Oxford slipped to a sixth consecutive League Two defeat at Rotherham.
Sean Rigg had put the visitors ahead early on when he shot through a crowd of players following a short corner.
But Rotherham soon took control as Ben Pringle and Lionel Ainsworth struck the woodwork for the home side.
Michael O'Connor scored from the spot after Michael Raynes felled Kayode Odejayi, before drilling in his second for 2-1, while Jason Taylor rounded off the win with a simple tap-in.
VIEWS FROM THE DRESSING ROOM
Rotherham United assistant manager Paul Raynor tells BBC Radio Sheffield:
"Delighted with three good points. It was a comfortable victory.
"We seemed to start sluggish, maybe we need to think about the way we warm up., because we're certainly not coming out of the blocks.
"To go a goal behind shows the character we have in the team.
"We got a grip of the game, tucked the penalty away, the crowd got behind us and there's only one winner for me after that."