Ryan Giggs, Wayne Rooney, Tom Cleverley and Frazier Campbell scored for the Red Devils, who outclassed the Amakhosi.
The English Premiership and European champions were the better team from the offset, but it was Kaizer Chiefs who produced the first real chance of the game when Siphelele Mthembu slipped the ball past Tomasz Kuszczak, but Nemanja Vidic cleared the ball off the line.
Siphiwe Tshabalala then hit a free-kick just wide in the 39th minute after Darren Fletcher fouled Jose Torrealba just outside the area.
United took the lead a minute later when Giggs scored into the top corner from a cross by Lee Martin.
The visitors almost doubled their lead two minutes later when Michael Carrick sent his header straight at Chiefs keeper Itumeleng Khune, following a good cross by Giggs.
Rooney made no mistake in the 57th minute when he ran clear of the Amakhosi defence to run onto a superb ball by rightback Danny Simpson, before slipping the ball through the legs of Khune to make the score 2-0.
Chiefs found themselves 3-0 down five minutes later when Rooney knocked down a cross by Simpson, for Cleverley to slot home at the near post.
Chris Eagles should have made it 4-0 in the 69th minute when he latched onto a loose ball inside the area, but the midfielder produced a tame shot which Khune saved comfortably.
Substitute Campbell also wasted a chance in the 82nd minute when he rounded Khune, but the united striker slipped allowing the Chiefs defence to clear the danger.
However, Campbell did manage to get his name on the scoresheet four minutes later when he latched onto a loose ball inside the area following Eagles’ failure to control a long clearance by Simpson, to slot home with a low drive into the far corner.
Paul Scholes had the ball in the back of the net in the 88th minute, but his effort was ruled out for an infringement on Khune.
The match ended with Manchester United deserved 4-0 winners, with Kaizer Chiefs a shadow of the side that went down 1-0 to the Red Devils in the opening fixture of the Vodacom Challenge at Newlands Stadium in Cape Town last Saturday.
Vodacom Challenge - Final (Kaizer Chiefs 0-4 Manchester United)