Goals from Barry Robson, Kevin McDonald and Dave Kitson helped the Blades make it three wins on the bounce and also arrest the string of home defeats.
Robson netted his first in a Blades shirt from the penalty spot after he was fouled by Colchester captain Josh Thompson. Kevin McDonald added the second, his first of the campaign, with a well-placed effort after the break in a game where Dominic Poleon, on loan from Leeds, made his debut and Diego De Girolamo came on for his league bow, setting up Dave Kitson's late tap in.
Robson made his first start for the Blades, replacing Forte, who failed to overcome a problem he picked up in midweek. New signing Poleon, whose loan capture from Leeds was completed before kick-off, took Robson's place on the bench.
It was quickly clear that the make up of United's offensive line had altered to accommodate the change in personnel - Murphy switched to a central role alongside Kitson, with Robson and Flynn supporting from the flanks and the latterly named duo did not take long to make an impact.
Little more than three minutes had elapsed when Flynn wriggled free down the left and delivered a low cross which Robson connected with just before being felled by Thompson. Referee Webb immediately pointed to the spot and newboy ROBSON took responsibility, drilling home the penalty. Colchester skipper Thompson, who gave away the penalty, sailed close to the wind on nine minutes when he challenged Murphy in the box, but this time the referee awarded a corner.
A neat move involving McMahon, Flynn, McDonald and Robson failed to create a chance but earned a round of applause from the crowd, whilst Colchester won a couple of free-kicks in decent positions and Thompson, Sears and Wright all failed to find the target with half-chances.
As well as being first scorer, Robson picked up the game's first booking, for a foul on Porter, before both goalkeepers were called into action in the space of a matter of moments. Firstly, Walker did well to hold a half-volley from Doyle and then Long managed to usher away a shot from Sears, which bounced just in front of him.
The Lane crowd were again appreciative when the Blades went close twice in the space of a couple of minutes, Firstly, Murphy's shot from the left channel was collected at the second attempt by goalkeeper Walker, who needed to be alert to drop on Kitson's intelligent flick from McDonald's cross.
Before the interval, Colchester could count themselves very fortunate not to be two or even three behind. On 44 minutes, Kitson headed home Robson's right-wing cross but was adjudged offside and then, in injury-time, after McDonald's enterprising run, Doyle smashed an unstoppable shot from 25 yards against a post.
In a quiet start to the second half both Flynn and Murphy had efforts blocked but the visitors caused one or two problems and Clifford fired over.
The second period was just 13 minutes old when Poleon was introduced, to replace Robson. The new boy headed for a central role with Murphy switching to a wide position.
McMahon was booked for a foul on Porter and as United failed to produce the rhythm of the first half, Higginbotham's poked clearance was only a foot wide of Long's goal.
However, it was the assistance of the Colchester defence that the Blades doubled the lead on 73 minutes. A stray pass landed at the feet of McDONALD 30 yards out and the midfielder advanced towards the edge of the box before slotting into the bottom corner of Walker's net.
As the game entered the final ten minutes, both Doyle and McMahon won tackles to set up a chance for Kitson, whose effort was blocked by Walker's legs. Higginbotham was the next to be denied by the goalkeeper, the left-back's curling effort pushed into the path of Flynn, who failed to take advantage.
The fourth official added four minutes after the allotted 90 and there was still time for more action and another goal. Deep into the extra period, McMahon chased down the right flank and pulled the ball back for De Girolamo - on moments earlier for Flynn - whose shot was blocked by Walker, but fell invitingly for KITSON to tap in from a yard.
Blades: Long, Higginbotham, Maguire, Flynn (De Girolamo 90), Doyle, McDonald, Kitson, Collins, Robson (Poleon 58), Murphy, McMahon.
Unused: Westlake, Hill, Ironside, McFadzean, Coyne.
Colchester: Walker, Da Wright (Bond 86), Garmston, Okuonghae, Sears, Ibehre, Massey (Dr Wright 72), White, Porter (Compton 60), Thompson, Clifford.
Unused: Morrison, Bean, Eastman, Phillips.