The Grecians made a terrible start and it was their own doing as they fell behind on seven minutes.
Goalkeeper Christy Pym saw a clearance charged down by Luke Berry and he ran out to atone for his error.
Pym then got in the way of team-mate Luke Croll, the two Exeter players leaving the ball for each other, and Berry took full advantage to nip in and roll the ball into the net from 25 yards.
On 10 minutes it was 2-0 and down to more awful defending. A long ball into the box was not dealt with and Harrison Dunk lashed a low shot past Pym from 18 yards.
Pym made a brilliant stop to deny Leon Legge and Cambridge substitute Adam McGurk dragged a shot wide after more error-prone Exeter defending.
Substitute Joel Grant gave Exeter hope when he headed in from Craig Woodman's cross on 73 minutes and Lee Holmes came close to an equaliser late on only for his short to be superbly blocked.
Reports supplied by the Press Association.
Match ends, Exeter City 1, Cambridge United 2.
Second Half ends, Exeter City 1, Cambridge United 2.
Foul by Robbie Simpson (Exeter City).
Leon Legge (Cambridge United) wins a free kick in the defensive half.
Pierce Sweeney (Exeter City) wins a free kick in the attacking half.
Foul by Ben Williamson (Cambridge United).
Substitution, Cambridge United. Sean Long replaces Brad Halliday.
Hand ball by Lee Holmes (Exeter City).
Will Norris (Cambridge United) is shown the yellow card.
Foul by Lee Holmes (Exeter City).
Piero Mingoia (Cambridge United) wins a free kick on the left wing.
Pierce Sweeney (Exeter City) wins a free kick in the defensive half.
Foul by Luke Berry (Cambridge United).
Pierce Sweeney (Exeter City) wins a free kick in the attacking half.
Foul by Luke Berry (Cambridge United).
Attempt blocked. Lee Holmes (Exeter City) right footed shot from the left side of the box is blocked.
Foul by Pierce Sweeney (Exeter City).
Ben Williamson (Cambridge United) wins a free kick in the defensive half.
Corner,  Exeter City. Conceded by Will Norris.
Attempt saved. David Wheeler (Exeter City) header from very close range is saved in the top centre of the goal.
Corner,  Exeter City. Conceded by Ben Williamson.
Corner,  Exeter City. Conceded by Mark Roberts.
Corner,  Exeter City. Conceded by Brad Halliday.
David Wheeler (Exeter City) wins a free kick on the right wing.
Foul by Greg Taylor (Cambridge United).
Goal!  Exeter City 1, Cambridge United 2. Joel Grant (Exeter City) header from the centre of the box to the bottom right corner. Assisted by Craig Woodman.
Ollie Watkins (Exeter City) wins a free kick on the left wing.
Foul by James Dunne (Cambridge United).
Substitution, Cambridge United. Ben Williamson replaces Uche Ikpeazu.
Foul by Lee Holmes (Exeter City).
Leon Legge (Cambridge United) wins a free kick in the attacking half.
Pierce Sweeney (Exeter City) wins a free kick on the left wing.
Foul by Adam McGurk (Cambridge United).
Attempt missed. Max Clark (Cambridge United) left footed shot from outside the box is close, but misses to the right.
Pierce Sweeney (Exeter City) wins a free kick in the attacking half.
Foul by Luke Berry (Cambridge United).
Attempt missed. Adam McGurk (Cambridge United) left footed shot from the left side of the box is close, but misses to the right.
Luke Berry (Cambridge United) is shown the yellow card for a bad foul.
Attempt saved. Piero Mingoia (Cambridge United) right footed shot from the centre of the box is saved in the centre of the goal.
Attempt missed. Robbie Simpson (Exeter City) header from the right side of the six yard box is close, but misses to the right.
Exeter slipped into the bottom two of League Two as they were beaten 2-1 by Cambridge at St James Park.