The result left United 12 points behind Chelsea, and Pompey in deep relegation trouble.
Both sides wore black armbands as a mark of respect for the death of Lomana LuaLua's son, who died of pneumonia. The DR Congo star wasn't told about the death until his team had been knocked out of the African Cup of Nations.
United started brightly and Ryan Giggs showed his class in the centre of midfield.
The Welshman beat three men on a mazy run, played a one-two with Ji-Sung Park and went round Dean Kiely, but his shot hit the bar.
Ruud van Nistelrooy showed his poacher's instinct to head in the rebound.
Ronaldo got in on the act as his fierce swirling shot beat Kiely all ends up and smashed into the roof of the net, to make it 2-0 after 38 minutes.
Pompey were all at sea at this point and apart from LuaLua the players weren't putting in enough effort.
Just before the break Wayne Rooney went on a diagonal run across the pitch and laid the ball off perfectly to Ronaldo.
The Portuguese winger's shot took a slight deflection off Andy O'Brien that deceived Kiely and the ball ended up in the net again.
United could afford to take off Giggs and Edwin Van der Sar at half-time, but Pompey showed more purpose in the second half as the visitors took their foot off the gas.
The hosts managed to force several corners as they began to exert pressure on the United goal and hopes of an unlikely, late rally were raised when Matthew Taylor headed in a Wayne Routledge cross in the 87th minute.
Pompey piled on the pressure for the final five minutes, but it was far too little, far too late.