Edged out at Charlton in their opener, before a midweek Carabao Cup exit at Championship side Plymouth, O’s paid their respects to the late Chris Bart-Williams before kick-off.
And there was a late change to their starting line-up, as Rob Hunt came into the side for Tom James, with Jayden Sweeney whipping in a dangerous cross in search of Joe Pigott on two minutes, which was just about cleared by Pompey.
Theo Archibald was looking lively on the wing for the home side, but neither side could create any clear chances in the opening exchanges.
Idris El Mizouni won possession well on 16 minutes and freed George Moncur, but he could not find Ruel Sotiriou on the edge of the box as the tempo began to rise.
And El Mizouni had claims for a free-kick on the edge of the box waved away after breaking through from midfield moments later, before firing over from Sweeney’s long throw-in.
Hunt made a vital block to deny Christian Saydee’s goalbound effort on 21 minutes, but the visitors took the lead two minutes later when Marlon Pack diverted a corner inside the far post.
Saydee sent a powerful shot over from the edge of the box, while Pigott just failed to get onto Archibald’s through ball and Sam Howes came off his line to beat Colby Bishop.
But Moncur’s well-struck shot forced Will Norris into a good low save five minutes before the break, before the midfielder was denied by a superb block from Regan Poole moments later.
Then just as O’s were sensing a way back, they conceded a second just on 44 minutes as Bishop headed home and Sotiriou fired at Norris in first-half stoppage time.
Bishop fired just wide within two minutes of the restart, with Wellens and Hunt booked in quick succession as the home side’s frustrations grew.
And things got worse for O’s on 51 minutes when Omar Beckles turned Gavin Whyte’s cross past Howes to hand Pompey their third goal of the game.
Sotiriou worked hard to get a shot away from the edge of the box just before the hour, which was deflected just over the crossbar.
But Howes had to get down well to his right to deny Whyte on 65 minutes, before Wellens made a triple change and saw one of the new arrivals – Max Sanders – go for goal from distance but fail to trouble Norris.
Jack Sparkes had a good chance for a fourth Pompey goal but shot wide from a tight angle on 75 minutes, while El Mizouni was not far away with a powerful shot at the other end and Charlie Pegrum flashed an effort just wide five minutes from time.
Sanders had a header held by Norris, before Pompey were awarded a penalty in stoppage time and substitute Kusini Yengi stepped up to convert and complete a miserable day for the O’s, who visit Wycombe on Tuesday.
Leyton Orient: Howes, Hunt, Sweeney (Turns 70), Happe, Brown (Graham 78), Pigott (Pegrum 70), Sotiriou, Archibald, Moncur (Sanders 70), El Mizouni, Beckles.
Unused subs: Byrne, Obiero.
Attendance: 8,372.
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