McDonald, a thorn in the side of the visitors all night at St. Andrew's, scored Blues leveller and went close to netting the winner late on, too.
It was a good response from Richard Beale's side in this PDL2 fixture; and they now move onto six games without defeat.
Colchester performed well and gave as good as they got. And they deservedly took the lead in first-half added-time, from a Elijah Phipps penalty.
But a couple of changes at the break and a forceful start to the second-half by Blues brought the equaliser, through McDonald with his third goal in as many games.
The first action of the game came when Ollie Kinsella got in front of Wes Harding but powered a diving header over the bar, from a good cross by Tommy O'Sullivan near the Kop corner flag.
Daniel Cleary headed wide from a floated free-kick in response, but his attempt never troubled Dillon Barnes in the Us goal.
Colchester constructed a move that almost brought them joy straight at the heart of the Blues defence but fortunately Tariq Issa's shot from 16 yards had the sting taken out of it after Logan Kwiecien got in close and the ball deflected off his heels.
The game's first save came in the 35th minute when Connal Trueman elected to take no chances and push away a tricky shot from O'Sullivan outside the area that bounced low just in front of him.
From the resulting corner the ball bounced about in the Blues area and Colchester were unlucky to see Ollie Kensdale's lash strike his own player, O'Sullivan, on the edge of the six-yard box.
Moments later Blues had a glorious chance to go ahead when a deep Mulders ball from the left found McDonald steaming in at the back post.
McDonald punched the ball down into the ground with his sidefoot and it reared up off the turf and over the bar.
Mulders dived in and did well to take the ball off O'Sullivan's toes after another of his clever runs, down the middle, was spotted by Kinsella, who biffed the ball forward into the open space in the centre of the area.
The half was finally beginning to hot up after a scrappy opening to the game, when Blues took plenty of time to adjust to the visitors' wing-back system.
On the stroke of the break Colchester broke the deadlock following a long, raking pass by Diaz Wright to the galloping Kinsella.
Olly McCoy was back with him at full tilt and made a sliding tackle which he claimed began just outside the area.
He got the man and ball, Kinsella's charge halted, and the referee pointed to the penalty spot.
Elijah Phipps calmly sent Trueman the wrong way with his kick, sliding the ball into the bottom right hand corner.
That was the last action of the first-half as the referee blew immediately afterwards and Blues were left to contemplate an unsatisfactory opening period.
Half-time: Blues 0 Colchester 1
The was a double change at the interval for Blues with Adams making way - on his first game back after a long injury lay-off - as well as Kwiecien. George O'Neill and Remeao Hutton entered the fray.
Harding moved to centre-half, Hutton went to right-back, while Lakin came inside as one of the sitting midfielders instead of Adams and O'Neill went to wide left of the three behind David Popa.
Within seconds of the restart McDonald raced down the left into the area and forced a parrying save from Barnes.
Then O'Neill strode into a similar area and dragged a left-footer wide of the target, but the ball was still alive as it rebounded back of the crowd of bodies to McCoy who sliced the follow-up high into the night.
Two good chances in quick succession suggested better things and more intent from Blues.
And sure enough in the 54th minute the lively McDonald robbed Ezechukwu Ebuzoeme on the blind side and surged on into the heart of the Us area.
Both Wright, Ebuzoeme as well the 'keeper tried to squeeze him out but McDonald's power, strength and persistence was rewarded when he forced the ball in from close range, despite their close attentions and challenges.
The goal sparked the Us into a furious period of sustained pressure, which Blues withstood doggedly.
A long ranger from McDonald relieved the attacks - Barnes got his body right behind the ball - before Blues made the final change: Matthew Timms replacing Mulders.
Blues still had to work to see the game out and extend their unbeaten sequence.
But on the break they also had good openings, working overloads into the area and shooting angles that were not always taken up.
A couple of times pull-backs from the wide area just fell short or to the wrong man.
And when O'Neill had a great chance to slide Timms through on the left, running down on goal, he underhit the pass allowing Kane Vincent-Young the opportunity to snuff out the danger.
With five minutes left McDonald came close to a winner with a fierce, dipping free-kick that although went straight over the wall and at Barnes the 'keeper still needed to use both hands to tip over.
From the subsequent corner, lofted to the far post, Cleary rose highest and got a strong header on target but Barnes was there again to make a fine save.
Blues finished the stronger side, forcing a string of corners, but were unable to find that second, decisive goal.
Blues: Trueman, Harding, Mulders (Timms 69), Baba, Cleary, Kwiecien (Hutton ht), McCoy, Charlee Adams (O'Neill ht), Popa, McDonald, Lakin. Not used: Weaver, Lubala.
Colchester: Barnes, Kensdale, Kinsella, Ebuzoeme (Brown 75), Peter, Wright, Vincent-Young, Phipps, O'Sullivan, Issa, Edge. Not used: Jones, Brown, Ogbodu-Wilson, Dunne.