Campbell emerged from his latest bout of injury misery to keep Sunderland's cup dreams alive at the Stadium of Light.
The former Manchester United striker was introduced as a half-time substitute, in the process making his first senior appearance since August 2010 as a result of two serious knee injuries.
He needed just 14 minutes to make an impact, sliding the ball past Boro keeper Danny Coyne from James McClean's pinpoint pass to cancel out Barry Robson's first-half opener.
The Black Cats had earlier seen a Craig Gardner strike controversially ruled out, but their Championship neighbours were good value for a replay after a full-blooded fourth-round contest in front of a crowd of 33,275.
Sunderland were dealt a major blow ahead of kick-off when skipper Lee Cattermole, who made his name as a teenager at Boro, was ruled out by a hamstring injury, a misfortune which was to prove significant before the break.
Gardner took his place in the middle of the field, but without Cattermole's bite, the Teessiders were able to prosper as Rhys Williams, Marvin Emnes and Robson, aided when not in possession by Faris Haroun and Scott McDonald, made life intensely difficult for their counterparts.
The visitors started brightly and Black Cats keeper Simon Mignolet was relieved to grasp McDonald's third-minute volley to his chest after it has initially threatened to squirm from his grasp.
Sunderland gradually worked their way into the game and might have gone ahead seven minutes later, only for Sebastian Larsson to head wastefully wide after Stephane Sessegnon had tricked his way past Robson and crossed from the right.
Boro had a lucky escape three minutes later when defender Seb Hines headed a David Vaughan corner straight at team-mate Haroun and saw the ball loop just over Coyne's crossbar.
But it was they who took the lead in spectacular style with 16 minutes gone.
Emnes made life difficult for defender John O'Shea, captaining Sunderland in Cattermole's absence, and he could only loop a weak header towards Robson on the left side of the penalty area.
The former Celtic midfielder needed no second invitation and unleashed a stinging volley which flew past Mignolet's despairing dive and into the bottom corner.
The travelling fans behind Coyne's goal were in raptures, but as the half wore on, it was they who started to see far more of the ball than they would have liked.
Coyne got down well to block McClean's 23rd-minute shot and was in the right place at the right time to claim the winger's close-range header seconds later.
However, the game erupted into controversy with six minutes of the half remaining after the Black Cats thought they had dragged themselves back into it.
Gardner controlled Kieran Richardson's cross with a hint of handball and fired home off the inside of the far post with striker Connor Wickham watching the ball home at close hand.
But the celebrations were ended abruptly by a flag, and after consulting his assistant, referee Kevin Friend ruled out the effort, apparently for offside against Wickham, despite the fact that he had not intervened.
Sunderland's mood might have darkened further on the stroke of half-time when Lukas Jutkiewicz found himself in on goal, but Mignolet saved his initial effort and when Haroun fed the rebound back to him, he fired harmlessly across goal.
Campbell replaced Wickham at the break, although it was Boro who enjoyed the better openings during the early exchanges.
Emnes volleyed just wide with 50 minutes gone and Robson curled a free-kick a yard past the post with the visitors refusing to sit on their lead.
The home side's fortunes took a turn for the worse when defender Wes Brown limped off after landing awkwardly following an aerial challenge with Emnes.
However, the 10 men levelled in stunning style as Michael Turner prepared to replace him.
McClean ran on to Robson's poor back-pass before squaring for Campbell, who slipped his shot unerringly past Coyne to send a sigh of relief around the stadium.
O'Neill's men tore into their opponents as the momentum swang firmly their way, although Boro continued to make a real fight of it.
Play switched rapidly from end to end, but neither side was able to find the killer blow in a rousing finale during which Williams was perhaps fortunate to see yellow rather than red for a wild challenge on Vaughan.