Boro boss Gareth Southgate has never won a North-East derby and despite seeing an early Habib Beye own goal put his side in front, Newcastle were always the better outfit.
In what was their biggest home win of the season, Steven Taylor levelled it up with a bullet header.
Then two goals in the final 20 minutes from substitutes Obafemi Martins and Peter Lovenkrands made it safe.
United's last home win was a 2-1 success against Spurs on 21 December, and since then they had only achieved an odd goal in five win against fellow strugglers West Brom at Tdhe Hawthorns.
Mark Viduka played in Owen who had a poor first touch but managed to spread the ball wide to Danny Guthrie who hopelessly screwed his effort wide.
But it was Boro who got the dream start with Newcastle pressing the self-destruct button after three minutes.
Kevin Nolan's poor clearance was picked up by Afonso Alves. The Brazilian played in Tuncay who was met by the lunging Steve Harper, only for the ball to hit Beye and end up in the net.
But within six minutes St. James' Park erupted with an equaliser from the fit-again Steven Taylor.
United won a corner on the right that was whipped in with pace by Guthrie and Taylor lost his marker to power a header across Brad Jones and high into the net.
In between United had almost drawn level when Viduka crashed a shot against an upright and Taylor put the rebound over the top.
Newcastle piled on the pressure but were almost caught out when Marvin Emnes - making his first Premier League start - was left in space. His swerving shot was beaten out by Harper and dropped invitingly back to Emnes, who shot wide with just the keeper to beat.
Boro suffered a setback when Alves was stretchered off after 34 minutes and was replaced by Marlon King.
Locked at 1-1 for the start of the second half, the scenario was quite clear - both sides had 45 minutes to have a chance of staying up.
And it was United who almost went ahead, Nicky Butt's raking crossfield pass finding the marauding Beye whose cross was flicked wide by Viduka.
Sloppy play from Harper put United under unnecessary pressure after 56 minutes and he was forced to redeem himself with an excellent block from Gary O'Neil.
Shearer then pulled off something of a masterstroke when he sent on Martins after 69 minutes for the woeful Owen and within 30 seconds the Nigerian had fired United in front.
A cross from the right was won in the air by Viduka for Nolan to backheel into the path of Martins, who despite slipping managed for force his shot beyond Jones.
Nolan then chased down a ball on the right and crossed for Lovenkrands to drill past Jones to make sure of a crucial victory.