Leeds suffered a third successive League defeat despite taking the lead in the first half through Robert Snodgrass's fourth goal of the season.
Colchester equalised on the stroke of half-time when Dean Hammond headed home Mark Yeates's corner.
The game turned in the second half as David Prutton earned a second booking for his foul on Yeates, who hit the winner from the resulting free-kick.
Last season's play-off finalists have now lost four games in a row.
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Sent Off: Prutton (65).
Booked: Prutton.
Goals: Snodgrass 34.
Colchester: Walker, Maybury, Coyne, Reid, Tierney, Yeates (White 86), Hammond, Izzet (Jackson 75), Perkins, Easter (Vernon 26), Platt. Subs Not Used: Gerken, Wordsworth.
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Booked: Reid.
Goals: Hammond 45, Yeates 66.
Att: 19,625
Ref: Nigel Miller (Durham).
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