O'Neil struck in the 54th minute to extend Pompey's unbeaten run to six games and keep Harry Redknapp's side on course for the Great Escape.
It took until the 11th minute for Pompey to show signs of the form that has rescued them from the brink of relegation.
Sean Davis picked out Andres D'Alessandro with a raking cross-field ball which the Argentine played across the penalty area for O'Neil, whose fierce right-foot shot was charged down by Andrew Taylor.
Brazilian midfielder Doriva had Middlesbrough's first meaningful attempt on goal seven minutes later when he fired over with a dipping 25-yard pile-driver.
Rookie central defender Matthew Bates came to Boro's rescue soon after when he stuck out a leg to divert Svetoslav Todorov's shot from the edge of the penalty area wide of Brad Jones' right-hand post.
Pompey had strong penalty appeals turned down midway through the half when Todorov appeared to be tugged back by Bates after being played in by Davis but referee Andy Marriner adjudged him to have slipped on the greasy turf.
Birthday boy D'Alessandro, who turned 25 on Saturday, came close to topping his big day with a first Premiership goal when he fizzed a shot inches wide of the left upright after cutting in from the left.
Yakubu, back at Fratton Park for the first time since a £7million move to Boro last summer, tested Pompey goalkeeper Dean Kiely's reactions with a long-range effort on the half-hour mark that the former Charlton keeper did well to hold.
Pompey had a narrow escape when Stewart Downing's 20-yard curler struck defender Linvoy Primus and flew into the side-netting.
Bates was then on hand to block Davis' powerful half-volley in 36th minute as Pompey continued to set the pace.
Jones produced the save of the first half to keep the scores level three minutes before the break. Bates blocked D'Alessandro's 30-yard strike but the ball fell kindly for Todorov and Jones came racing out his goal to save the Bulgarian's close-range shot with the legs.
Home captain Dejan Stefanovic thought he'd opened the scoring from the resulting corner but his header was ruled out for a push.
Kiely matched Jones' heroics at the other end of the field when he blocked Yakubu's near-post effort in first-half stoppage time.
Pompey took the lead nine minutes after the restart when O'Neil hammered in his seventh goal of the season. Benjani Mwaruwari burst his way into the Boro penalty area before Todorov stole the ball off his toes and played in O'Neil who fired past Jones and into the bottom left-hand corner from 12 yards out.
Jones denied Pompey a second minutes later when he stole half-time substitute Wayne Routledge's inviting cross from the head of Todorov.
Substitute Malcolm Christie should have had double-chasing Boro on level terms on the hour mark when he seized on a slip by Matt Taylor but scuffed his shot straight at the grateful Kiely.
O'Neil threatened to add a second in the 67th minute when he unleashed a fierce right-footed shot from the edge of the area which Jones managed to beat away.
Substitute David Wheater almost ruined Pompey's day in the dying seconds when he wriggled free to reach Downing's late corner only to blaze wide from two yards out.