The hosts went ahead in the first half, with Murray scoring after only five minutes.
After a host of chances went begging for the U's in the first period, Sears equalised midway through the second half but the hosts scored immediately to make it 2-1.
The home side then had two men sent off late on in the game but the U's couldn't capitalise, despite being encamped in the County half.
U’s skipper Magnus Okuonghae was restored to the starting line-up, following his one match suspension for the red card picked up at Charlton.
He replaced Frankie Kent at centre half, with Dominic Vose replacing Gavin Massey in the front three.
Massey and Kent dropped down to the bench and they were joined by Craig Eastmond, who had recovered from his ankle injury sustained on the opening day of the campaign.
The game started with the home side on the front foot and Sam Walker had his first involvement within the first minute, saving comfortably from Noble.
His next involvement was unfortunately picking the ball out of his net, as Ronan Murray opened the scoring.
A speculative shot came in from outside the box, which was flying off target, was turned in by the County striker, who looked lucky to get the touch goalwards.
From then on in the first half, it was all Colchester United, and the first of a host of efforts was headed over by Jabo Ibehre as Ben Gordon’s cross came in from the left.
With quarter of an hour gone, the U’s striker then had a double chance but was denied by Roy Carroll before heading wide.
Another double chance came a minute later, with George Moncur having a shot deflected over and Magnus Okuonghae heading close enough to the home keeper for him to save.
Dominic Vose and Freddie Sears then hit long range efforts over after two good passing moves by the now dominant visitors.
Another chance went begging, with midfielder Marcus Bean getting in the act, heading wide from a corner from Moncur.
Vose shot straight at the keeper on the half hour, and then Ibehre was denied by a great save by the left foot of former Manchester United keeper Carroll.
The best passing move of the game came in the thirty sixth minute, but the finish from Moncur was once again sent over the bar.
A thirty yarder from Sears followed suit, before Tom Eastman headed over with the last chance of the half.
It would have been a tough team talk for the U’s boss at half time, with is players giving him a fantastic display of attacking football.
Only a finish at the end of the flowing football was missing, something that the U’s looked to put right.
It took them almost fifteen minutes to create the first opening after the break, with Sears denied by another great save from Carroll.
Ben Gordon started the move down the left, Vose was instrumental as he found Sears in space but Carroll was quick out to block the shot.
A long range effort from Alex Gilbey went over on sixty eight minutes but the U’s got their equaliser a minute later.
Sears once again got clear of the home defence and calmly slotted his shot through Carroll’s legs to make it 1-1.
It was no more than the U’s deserved, but the good work was undone less than ninety seconds later, with County going ahead once again.
There didn’t look to be any danger as Noble picked the ball up forty yards from goal, but he advanced a few yards before curling a stunning effort into the top corner.
With fourteen minutes left, the hosts were reduced to ten men, with young full back Keane getting his marching orders after his second yellow card.
Gavin Massey and Sammie Szmodics were introduced for Vose and Bean but the U’s continued to see chances go begging.
The impressive Moncur struck a superb volley inches wide, and then hit another shot too close to Carroll.
Another Notts County player was off with a few minutes left on the clock, as Wroe got his marching orders for a second yellow.
He had kicked out at a U’s player for is first and then lobbed Walker long after the whistle had gone for an offside, giving the official no choice but to send him off.
In injury time, Sears had the final chance but his effort went narrowly wide, leaving the U’s bitterly disappointed with a defeat after a stunning away performance that didn’t get its just rewards.