The home side started well and created some decent chances to go in front. The best of those saw Jamie Cureton crash a volley against the underside of the crossbar, but for all their early dominance, Paul Tisdale's men could not break the deadlock.
As it was, Oxford scored with their first genuine attack. Exeter were slow to react in midfield and when Tom Craddock lobbed the ball forward, James Constable shrugged of his marker and turned well before lashing a shot past the static Artur Krysiak.
Craddock and Constable both missed great chances to double Oxford's lead, but the U's wrapped up the points with two quick goals shortly after half-time. Constable capitalised on Pat Baldwin's poor header to roll in the second from 18 yards and Peter Leven drilled a fine low short into the far corner from similar range.
Exeter pulled one back on 67 minutes when Cureton netted from the spot after a handball by Damian Batt.