Their more experienced crew were in front from the start and finished comfortable winners to end a run of three successive defeats.
As usual in an Olympic year, both crews were under strength, with leading rowers preparing for Rio instead, although Cambridge still fielded three Americans, one German-American and one Austrian in their eight.
Their coach Steve Trapmore, who won a gold medal in Great Britain's eight at the 2000 Olympics, said it was an "epic" victory given the conditions.
"I've never felt prouder," he told the BBC.
"We're all sad," Oxford cox Sam Collier said. "We threw everything we had at it but the conditions played a part. It was a tough one."
Earlier, Oxford easily won the 71st edition of the women's race, now held over the same course, after the Cambridge boat took on water and almost sank.
