The Bees would have felt aggrieved not to enter the half-time interval with an advantage after they mustered several chances in the first-half.
The best fell to Sergi Canos, who was slipped in beautifully by Ivan Toney, only for David De Gea to deny his compatriot with an excellent save with his foot.
But the Red Devils stepped up their game in the second stanza as Anthony Elanga broke the deadlock ten minutes after the break.
United took full advantage of the change in momentum by going ahead 2-0 just six minutes later.
The Portuguese strode forward rapidly before squaring a pass to Mason Greenwood for a simple tap-in.
Ronaldo was replaced with Harry Maguire for the final 15 minutes and the veteran forward was furious with Ralf Rangnick's decision.
But the German was proved correct when fellow substitute Marcus Rashford scored with an excellent first-time finish to put United ahead 3-0.
Brentford got a deserved goal late on through Ivan Toney but it proved little more than a consolation for Thomas Frank's side.
Speaking after the game, Elanga thanks Rangnick for showing him faith in recent weeks.
He toldBT Sport: "The first touch set it up. I could see the keeper coming and I just had to head it in.
"I want to continue to work hard and get more goals. I appreciate the boss so much. You can see the intensity we put in in training and can see that if you put in that work you get the results you deserve."
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