The 41-year-old former England and Manchester United star brought a touch of class to an error-ridden encounter as Sheffield Wednesday slipped to their first defeat in seven.
Sheringham struck after just 52 seconds and rifled in a low shot as Wednesday - hampered by the absence of Yoann Folly and Michael Johnson - struggled.
Wednesday had a difficult start to the day when midfielder Folly was given the day off because of a serious family illness and Glen Whelan replaced him.
And in the pre-match warm up centre-back Michael Johnson injured his back and rookie Mark Beevers, 18, was promoted from the bench.
And with less than a minute on the clock veteran Sheringham showed all his guile and experience to give the visitors the lead that stunned the home crowd.
He drifted in from the left, unchallenged and drilled a typical low angled shot wide of Lee Grant for his third goal of the season.
Four minutes later Marcus Tudgay had a chance to level, but his header from Burton O'Brien's astute cross was over the top.
Thinks got worse for Wednesday after 25 minutes when Colchester punished the home side's dismal defending with a second goal.
Frank Simek allowed the ball to run out believing it was a goal kick, but held his head in his hands when Colchester were handed a corner.
Mark Yeates crossed the ball to the far post where left-back George Elokobi rose unmarked. His header went down at his feet but he stabbed the ball from close range.
Whelan shot wide as Wednesday began to find their feet, but then Akpo Sodje claimed his fifth goal in six outings when he clipped the ball in from close-range after great work by Jermaine Johnson and Whelan.
Mark Yeates should have done better after 59 minutes when he found himself in space to meet a low cross from Kevin Lisbie but his shot was blocked and ran for a corner and at the other end a Johnson shot was easily saved.
A deft flick from Sheringham had Wednesday in trouble, but Elokobi couldn't squeeze it in and keeper Lee Grant managed to gather the ball.