The U's led at half-time through Piero Mingoia but the game was transformed by goals from Shrimps pair Jack Dunn and Paul Mullin in the space of three minutes after the hour.
Winger Mingoia opened the scoring nine minutes before the break, firing across Morecambe goalkeeper Barry Roche after the ball fell to him when Ben Williamson was unable to get a shot away.
The visitors levelled in the 62nd minute when Dunn converted from the penalty spot after being brought down by Luke Berry.
Dunn was involved again two minutes later, robbing Conor Newton and freeing Mullin down the middle, who rounded keeper Will Norris and fired beyond a man on the line.
Medy Elito and Berry both fired wide as the hosts failed to find an equaliser, leaving them without a win in their opening eight league fixtures.
Cambridge United manager Shaun Derry told BBC Radio Cambridgeshire:
"Until I'm told otherwise I'll be doing my job exactly the same as what I've been doing for the last 10 months.
"It's been a job that I'm very proud to have. I've enjoyed some wonderful times here and I expect to enjoy some future wonderful times.
"I'm a fighter. I feel like I'm in a little war at this moment in time, a war with myself as well as I hate seeing us at the bottom of the league. But I'm fighting."
Report supplied by Press Association.
Match ends, Cambridge United 1, Morecambe 2.
Second Half ends, Cambridge United 1, Morecambe 2.
Attempt missed. Adam McGurk (Cambridge United) right footed shot from outside the box is too high.
Attempt missed. Jack Dunn (Morecambe) left footed shot from outside the box is high and wide to the left.
Uche Ikpeazu (Cambridge United) wins a free kick on the right wing.
Foul by Michael Rose (Morecambe).
Ryan Edwards (Morecambe) wins a free kick in the attacking half.
Foul by Harrison Dunk (Cambridge United).
Attempt saved. Uche Ikpeazu (Cambridge United) right footed shot from outside the box is saved in the bottom left corner.
Substitution, Morecambe. Aaron McGowan replaces Paul Mullin.
Brad Halliday (Cambridge United) wins a free kick in the defensive half.
Foul by Michael Rose (Morecambe).
Substitution, Cambridge United. Greg Taylor replaces Medy Elito.
Attempt missed. Luke Berry (Cambridge United) right footed shot from outside the box is just a bit too high.
Attempt blocked. Uche Ikpeazu (Cambridge United) right footed shot from the centre of the box is blocked.
Dean Winnard (Morecambe) is shown the yellow card for a bad foul.
Uche Ikpeazu (Cambridge United) wins a free kick in the defensive half.
Foul by Dean Winnard (Morecambe).
Foul by Medy Elito (Cambridge United).
Paul Mullin (Morecambe) wins a free kick in the attacking half.
Substitution, Morecambe. Ntumba Massanka replaces Cole Stockton.
Substitution, Morecambe. Peter Murphy replaces Andrew Fleming.
Brad Halliday (Cambridge United) wins a free kick in the attacking half.
Foul by Cole Stockton (Morecambe).
Harrison Dunk (Cambridge United) wins a free kick in the defensive half.
Foul by Cole Stockton (Morecambe).
Attempt missed. Medy Elito (Cambridge United) right footed shot from the left side of the box is close, but misses to the right.
Attempt saved. Max Clark (Cambridge United) left footed shot from outside the box is saved in the centre of the goal.
Attempt saved. Jack Dunn (Morecambe) left footed shot from outside the box is saved in the centre of the goal.
Corner,  Morecambe. Conceded by Leon Legge.
Foul by Uche Ikpeazu (Cambridge United).
Dean Winnard (Morecambe) wins a free kick in the defensive half.
Substitution, Cambridge United. Max Clark replaces Conor Newton.
Substitution, Cambridge United. Uche Ikpeazu replaces Ben Williamson.
Goal!  Cambridge United 1, Morecambe 2. Paul Mullin (Morecambe) left footed shot from the centre of the box to the top left corner. Assisted by Jack Dunn.
Corner,  Cambridge United. Conceded by Dean Winnard.
Goal!  Cambridge United 1, Morecambe 1. Jack Dunn (Morecambe) converts the penalty with a left footed shot to the bottom left corner.
Penalty conceded by Luke Berry (Cambridge United) after a foul in the penalty area.
Penalty Morecambe. Jack Dunn draws a foul in the penalty area.
Attempt missed. Cole Stockton (Morecambe) right footed shot from more than 35 yards is too high.
Cambridge's dismal start to the League Two season continued as they surrendered the lead to lose 2-1 at home to Morecambe.