The 22-year-old Italian, signed on loan from Liverpool, struck with an 85th-minute pile-driver to secure just a second home league win for the Black Cats over their neighbours since 1980 and a first in the league this season.
His intervention came as the Magpies looked for a winner of their own after Mathieu Debuchy had dragged them back into the game with a 57th-minute equaliser, his first goal for the club.
Steven Fletcher had headed the home side in front with just five minutes gone as Gus Poyet's men made light of their recent difficulties in his first home game at the helm in front of a crowd of 46,313.
But their commendable efforts to deny Newcastle time and space dwindled as they rather ran out of steam and with Cheick Tiote and Yohan Cabaye finally starting to get to grips with the central midfield battle, it was the visitors who looked the more likely winners as time ran down.
However, Borini thought otherwise and his timely intervention handed Poyet a derby victory in his second game in charge to match predecessor Paolo Di Canio's achievement.
It was a match Sunderland simply could not afford to lose for a variety of reasons and they went about their task with some relish.
The absence of a recognised centre-half pairing for the Magpies - neither Fabricio Coloccini or Steven Taylor was able to plug the gap left by the suspended Mapou Yanga-Mbiwa, placing the onus on specialist left-back Paul Dummett - gave the Black Cats an opportunity, and it was one they were to exploit within minutes.
Poyet opted to pair Fletcher with summer signing Jozy Altidore and the pair caused Dummett and partner Mike Williamson all kinds of problems in a high-octane start by the home side.
They needed just five minutes to force their way in front, and the goal came straight from the training ground.
It was the perfect start to Poyet's first game at the Stadium of Light and for 20 heady minutes or more, Sunderland dominated proceedings with Lee Cattermole leading the fight from central midfield and his team-mates following suit.
Johnson repeatedly made ground down the left and delivered a series of telling crosses, Fletcher glancing a 14th-minute header wide from one of them three minutes before forcing Tim Krul into a save with a well-struck effort from distance.
Magpies boss Alan Pardew, who had started as he did against Liverpool last week with Hatem Ben Arfa at the pinnacle of 4-2-3-1 formation, was forced to abandon Plan A with his team simply not competing, and with Loic Remy moved into an advanced position and Ben Arfa dropping deeper, Newcastle were far more effective.
However, all their better attempts came from distance with Cabaye prompting Keiren Westwood to make his only real first-half save with a dipping 16th-minute free kick, but both he and Ben Arfa were significantly more wayward thereafter.
Perhaps the Magpies' most promising attack of the opening 45 minutes came eight minutes before the break when left-back Davide Santon picked out right-back Debuchy with an elegant pass and Larsson had to head his dangerous cross away with black and white shirts arriving in numbers.
Pardew opted for further change at the break, sending on striker Papiss Cisse for midfielder Moussa Sissoko, but the Magpies were able to create little during the opening exchanges of the second half despite enjoying a wealth of possession.
But they were back in it 12 minutes after the restart when Ben Arfa, who had been infuriatingly ineffective until that point, accepted Cabaye's pass and drove a low cross across the face of goal for Debuchy to convert at the far post.
Cabaye fired just wide after good work by Santon and Ben Arfa with 63 minutes gone with the visitors starting to turn the screw.
However, Borini almost made his name on Wearside within seconds of his arrival as a 69th-minute replacement for Johnson, blasting a shot through Krul, only to see the Dutchman gratefully grab the ball at the second attempt.
Santon drilled a skidding effort just wide with 14 minutes remaining and derby specialist Shola Ameobi, on as a 70th-minute replacement for Remy, went just as close two minutes later.
But the decisive moment came at the other end five minutes from time when Borini ran on to Altidore's lay-off and smashed an unstoppable shot past Krul to win it.