James Constable fired a double to boost Oxford United's play-off hopes in a match that saw Grays goalkeeper Rob Beckwith taken to hospital with a suspected depressed cheekbone.
Kevin Sandwith and Adam Chapman both scored their first goals for the club as Chris Wilder's team chalked up their biggest win of 2009.
But Constable really should have had a hat-trick, missing three gilt-edged chances to get his third.
It was a nightmare day for Grays who, as well as losing 24-year-old Beckwith with a serious injury that caused a 16-minute stoppage in the first half, also had Stuart Elliott sent off before the break.
Kevin Sandwith, selected at left back ahead of Chris Carruthers, and making his full home debut, opened the scoring in the seventh minute when a free-kick by Adam Murray got caught under a defender's foot, leaving him with a simple tap-in.
Adam Chapman made a vital block, and Constable cleared from virtually off the goalline as Grays tried to hit back, and they probably fancied their chances with Billy Turley troubled by his shoulder injury after trying to deal with a corner.
Constable was glad to see a flag up for offside when he somehow headed wide from two yards after good work by Yemi Odubade, but Oxford's leading scorer soon got into gear.
He made it 2-0 on 26 minutes with good anticipation from a long clearance by Turley. Beckwith hesitated in coming out and the U's striker stuck out a leg and diverted it past him and into an open goal.
On-loan Hereford winger Bradley Hudson-Odoi had sa drive beaten out by Turley after cutting in from the left before the Essex side were reduced to ten men five minutes before the interval.
Elliott had been yellow-carded only a few minutes earlier, and when he then fouled Murray just yards from the ref, the official lost his patience and pulled out another yellow, followed by a red.
It was clear soon after it happened, that the injury to Beckwith was a bad one.
Lewis Haldane's knee accidentally connected with his head after visiting defender Rob Gier left the ball to the keeper.
Beckwith, who was making only his third appearance for the club, was knocked unconscious by the impact, and with worries that he may have seriously injured his neck as well, medical staff took every precaution they could before lifting him onto a stretcher.
He did regain consciousness, though, before being taken by ambulance to the John Radcliffe Hospital.
The injury caused one of the longest hold-ups to play ever known at an Oxford United match.
And with countless other stoppages for minor injuries all over the pitch - Chris Willmott and Luke Foster both had to put on replacement numberless shirts because of bleeding and Damian Batt needed treatment following a clash of heads - the first half lasted 71 minutes!
The half-time whistle eventually went after Constable had made it 3-0, turning in Yemi Odubade's driven right-wing cross.
Constable scuffed an angled shot after charging down a clearance at the start of the second half before Oxford took off Adam Murray, who has been troubled by a foot injury, and sent on Craig Farrell.
Tony Dinning drove in a 19-yard free-kick given away by Chris Willmott to pull a goal back for Grays.
But Chapman restored the home side's three-goal advantage with a glorious goal, a classy left-foot finish from 16 yards from Farrell's pass.
It could easily have been more goals. Chapman was unlucky with a volley and only a poor first touch twice prevented Constable getting his third.
Oxford Utd: Turley, Batt, Willmott, Foster, Sandwith, Odubade, Chapman, Clist, Haldane (Carruthers 67), Murray (Farrell 59), Constable. Subs not used: Day, Hinchliffe, Hutchinson. Booked: Clist.
Referee: Matt McLaughlin (Beds).
Att: 4,764 (63 from Grays)
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