The Red Devils made it four wins from their opening four Group F fixtures after coasting to the points against a side whose game-plan to defend in numbers was left in tatters by two first-half strikes within the space of six minutes.
Gerard Pique and Carlos Tevez fired the home side into a 2-0 half-time lead, before further strikes from Wayne Rooney and Cristiano Ronaldo completed the scoring after the interval.
Sir Alex Ferguson had made five changes to the side that drew with Arsenal at the weekend with Pique, Michael Carrick, Nani, Darren Fletcher and Danny Simpson all drafted into the starting line-up.
But despite the changes in personnel, United coasted to the most comfortable of European victories against a side that only showed attacking endeavour when they had fallen two goals behind.
United broke the deadlock in the 31st minute when Pique scored his first goal for the club.
Ronaldo's free-kick was glanced goalwards by Carrick but, after the ball struck the unwitting Tevez on the back of the head, it looped up invitingly for the Spanish defender to nod home at the far post.
Tevez doubled the advantage six minutes later when he picked the ball up in midfield and played a one-two with Rooney before lashing home a powerful shot from just inside the area.
The visitors made a double attacking change at half-time by sending on Serhiy Rebrov and Diogo Rincon.
United were also forced into a change when goalkeeper Edwin Van der Sar was forced off with a foot injury and Tomasz Kuszczak was called into action.
Kuszczak was forced to beat away a Rincon drive as Kyiv cast off their early defensive shackles in the opening moments of the second half.
Marjan Markovic then sent over a cross that Rincon was inches away from converting at the back post as United suddenly found themselves on the back foot.
But as the game began to open up, the home side took full advantage and Olexandr Shovkovskiy was forced to make a double save from Tevez and Simpson before United finally put the game out of reach in the 76th minute.
Nani looked up and saw Rooney unmarked in the box, and when the cross came in, the England striker calmly side-footed home on the volley from eight yards to make it 3-0.
Ronaldo then set the seal on the victory with a superb fourth in the 88th minute.
The Portuguese winger roared into the penalty area and neatly flicked the ball onto his right foot before picking his spot beyond the keeper with a powerful rising drive into the far corner of the net.