Oxford's fourth successive victory in the Varsity Match was marred by the first red card in the fixture's 141-year history.
The Dark Blues dispatched Cambridge 33-15 but had to play most of the second half with 14 men after scrum-half Sam Egerton was sent off for an incident at a ruck involving flanker Nick Viljoen.
Referee Matt Carley dismissed Egerton in the 51st minute on the advice of the television match official shortly after the half-back had scored a try.
Even when down to 14 men Oxford were under little threat as they romped to a record-equalling fourth consecutive win in the 132nd meeting between the rivals.
John Carter, Henry Lamont and Nicholas Gardner also crossed for the Dark Blues, while John Hudson kicked three penalties and two conversions.