The sending off of midfielder Gary Donnellan brought to a close an electrifying first half which saw six goals in 36 pulsating minutes. McDonough quickly brought the 2,226 crowd to life in the fifth minute as he snapped up the leftovers when Gary Bennett's close quarter effort from an Eamonn Collins cross was palmed up in the air by Trevor Bunting.
But the Rebels lashed back: a minute later when the heroic Steve Thompson, drove to the bye-line and pulled back a low cross for new-signing Eamonn O'Connor to drill home on the volley.
And it was Thompson again who put the Rebels in front in the 12th minute, tidying up after £18,000 signing from Farnborough, Colin Fielder, planted his shot against a disorganised defence.
The U's got back on level terms from a corner in the 23rd minute, McDonough unimpeded at the near post for a simple conversion of Nicky Smith's inswinger.
The striker got his hat-trick in style, Steve McGavin's brilliant snapshot from 30 yards out hitting the underside of the crossbar with McDonough at the far post to tap home in the 28th mmute. And McDonough made it four in the 41st minute when he threw himself headlong at McGavin's cross from the left to power home.
With full back Phil Stacey already in the book for a late tackle on Smith in the 33rd minute, Donnellan then got his marching orders after elbowing Shaun Elliott in the face as tempers flared at the and of the half.
McDonough, now sporting an bloody eye wound, had three good chances early soon after the break to surpass Martin King and Bobby Hunt's four apiece against Bradford back in 1963. But his best, a lob in the 51st minute to beat the stranded Bunting, slithered slowly past the far upright.
The game, unable to sustain its sensational pace and incident, went into a simmer with the U's controlling the midfield with short, crisp man-to-man possession.
If there was a lesson for the new-look, new-feel Rebels, it was this — Colchester did the simple things and did them well.
Switching the tension from side to side with equally accurate crossfield deliveries the U's never looked like surrendering their lead while the Rebels still betrayed a tendency to give the ball away in unforced situations.
Both defences must also shoulder the blame for four of the goals. Slough wrestled with further problems as Thompson went into the book for a foul on Warren Donald, but on the whole look more solid this term.
Allan Pluckrose looked the best of the five new boys on show, combining well with Thompson on the left to get over a couple of promising crosses. A potent striker of McDonough's class might have converted these, but there still looks to be a vacancy for that slot at Slough.
Sutton-signing Paul McKinnon might turn out to be the man for the job, but having missed out on the preseason still lacks the match fitness to prove his worth. Centreback Mick Putnam often managed to get the better of McDonough in the air and will be an asset in both defence and attack.
Colchester Utd Line up
Barrett, Donald, Grainger, Kinsella, English, Elliott, Collins, Bennett, McDonough, McGavin, Smith. Subs: Phillips (for Elliott), Abrahams (for McGavin).