The 32-year-old recorded his ninth win in 12 years, and his first since 2012, the year he also won Olympic bronze in London.
Enniskillen's Holly Nixon finished an impressive second in the women's single sculls at Caversham.
Peter Chambers and Joel Cassells were second in the men's lightweight pair.
Campbell started quickly and built a lead which he maintained throughout to lead home Graeme Thomas in second place.
"I'm very happy with that," he said.
"I'm hugely relieved. It's a hard, tough race, probably the hardest of the year, and it feels like a collective weight has been lifted.
"Now we can get on with forming crews and doing what has to be done this summer.
"I know where I want to be and I have put myself in a good strong position."
Nixon made the 'B' final of the women's single sculls twelve months ago but this was a big step up the ladder for the 22 year-old member of Portora Boat Club, as she finished second behind Vicky Thornley.
Great Britain have yet to qualify for Rio in the women's single sculls or women's quadruple sculls and the final qualifying regatta will be held in Lucerne in June, with Nixon now hopeful of selection.
The selection for the men's lightweight four promises to be just as tight.
Coleraine's Peter Chambers and Joel Cassells won the European title last year in the men's lightweight pair but were beaten into second place by Sam Scrimgeour and Jonno Clegg in a tight finish on Wednesday.
Richard Chambers missed the trials because of a hand injury but is expected to be selected alongside Will Fletcher, who won the lightweight single sculls.
The duo won silver at the 2015 World Championships in France in the lightweight double sculls.
Coleraine's Alan Campbell remains on course for a place at a fourth Olympic Games after winning the men's single sculls at the GB Rowing trials.