An inch-perfect goal from Ruud van Nistelrooy gave United the lead before Cristiano Ronaldo scored a brace to wrap up the game by half time, while Matthew Taylor headed a late consolation goal for Portsmouth.
With this result, Man United maintained their second-place position with a tally of 54 points, 12 points behind leaders Chelsea, while Liverpool linger in third place with 48 points.
Van Nistelrooy put United up front after playing a quick one-two with Ryan Giggs before rounding Portsmouth’s Dean Kiely and heading in a rebound shot that hit the crossbar in the 18th minute.
Ronaldo doubled the Red Devils’ lead with a goal in the 38th minute after collecting a loose ball at the edge of the box and firing the ball straight into the roof of the net.
The Portuguese star scored his second goal after he connected a Wayne Rooney shot and stormed into the area before scoring the winner right before half-time.
Taylor managed to save face for Pompey with a great header in they dying minutes of the match.
Portsmouth come as second from the bottom with a tally of 18 points.