However, whereas Carlos Tevez, Ryan Giggs and Michael Carrick all kept their nerve in the shoot-out and scored, Lassana Diarra, Arnold Mvuemba and Glen Johnson all failed with their efforts as United prevailed 3-1.
Last season Pompey had beaten United 1-0 at Old Trafford in the FA Cup quarter-finals before going on to secure the trophy in May and they again frustrated Sir Alex Ferguson's side, without Cristiano Ronaldo and Wayne Rooney, for long periods.
Gary Neville captained United after finally recovering from his 18 months of injury problems while Peter Crouch teamed up with Jermain Defoe in Pompey's attack following his switch from Liverpool.
The first half was a lack-lustre affair though with the best opening falling to Darren Fletcher in the 35th minute.
Nani dispossessed Johnson, who endured a woeful afternoon, before crossing for the Scot who somehow failed to get a good connection on the ball as he slid in when it seemed easier to score.
The match continued to be a mundane affair after the break although United created enough chances to win the game comfortably.
In the 50th minute James punched a corner to Fletcher whose flicked shot came back off the crossbar with the veteran Pompey shot-stopper stranded.
Twenty minutes later James made a superb stop when he dived full-length to turn the outstanding Tevez's effort away for a corner.
The Argentinian should have had a penalty with 15 minutes remaining when he appeared to be hauled down by Hermann Hreidarsson inside the area but the referee was unimpressed and waved play on.
Tevez was lucky not to be shown a red card when he grabbed the Icelandic defender by the throat in the aftermath of the incident.
Edwn van der Sar only had one save to make - from John Utaka's speculative 78th-minute long-range effort - but justice was done in the end as United succeeded in the shoot-out.