Pompey themselves helped hammer some of the nails into their coffin with own goals by Anthony Vanden Borre and Marc Wilson, while a deflection off Richard Hughes assisted United's third goal.
Yet the Premier League's bottom club had two good chances before United opened the scoring.
United goalkeeper Edwin van der Sar made a fine save from Anthony Vanden Borre's fierce 13th minute shot, while Jonny Evans cleared Nadir Belhadj's 28 minute drive off the line.
But, in the end, it proved to be a case of champions against the seemingly doomed and men against boys.
Portsmouth's marking was woeful in the 40th minute when Darren Fletcher crossed from the right and Wayne Rooney nipped in between two defenders and goal keeper David James to head home from four yards.
It was Rooney's 21st league and 23rd goal of the season and the England star played his part in the second goal in the dying seconds of the first half.
Rooney's crisp pass found Nani on the left side of the Portsmouth box and his speculative shot from ten yards was deflected off Vanden Borre into the net, with James also getting a touch before the ball crossed the line at the near post.
Things went from bad to worse for Pompey in the 59th minute when Michael Carrick's 22-yard shot was deflected in off Hughes, with the ball going in off the underside of the bar.
United's best goal of the game was their fourth after 62 minutes.
Dimitar Berbatov, who missed a first-half sitter from six yards, showed magical skillwhen he toyed with Tal Ben Haim in the Pompey penalty area before scoring with a low shot from 15 yards.
Pompey's troubles were encapsulated in United's fifth goal in the 69th minute.
Nani headed on Patrice Evra's cross from the left and Wilson hammed the ball into the roof of his own net from six yards.