The hosts were in control of the game right from the start at Elland Road and went ahead in the 26th minute.
Jamaica international Rodolph Austin scored with a ferocious drive from 20 yards from Aidy White's pass.
Eight minutes later Neil Warnock's side doubled their advantage when Samuel Bryam chipped Oxford goalkeeper Ryan Clarke from just 10 yards.
Austin continued to impress in the second half, as he rattled the visitors' crossbar from 40 yards.
Tom Lees eventually wrapped up the victory for Leeds in the 74th minute when he headed home El-Hadji Diouf's delivery.