Steve Harmison and Graham Onions took eight wickets between them as Durham skittled out Lancashire for 135 to win by 138 runs inside three days.
The impressive Harmison took the first four wickets of Lancashire's second innings to end with figures of 5-46.
Onions dismissed Andrew Flintoff to leave Lancashire in trouble at 64-5 and the home side eased to victory.
Durham had resumed their second innings on 122-6 but added just 23 runs, Saj Mahmood taking three of the wickets.
Mahmood, who like Harmison is hoping to force his way back into the England reckoning, finished with career-best figures of 6-30.
Ian Blackwell was first to go, caught and bowled for 74 and Mahmood then had both Mitch Claydon and Callum Thorp caught in the slips.
The last wicket went to Flintoff when his close friend Harmison was wonderfully caught by Francois Du Plessis on the boundary.
But on a two-paced pitch that offered plenty of encouragement to the pace bowlers, Lancashire were never likely to chase down the 274 runs they needed for victory in their second innings.
Harmison's wayward opening over cost 10 runs, but he soon found his rhythm and direction and had Paul Horton caught behind in his second over.
South African Ashwell Prince followed Horton after being given out lbw by umpire Neil Mallender and Du Plessis fell just before lunch when he edged another good ball to Phil Mustard.
Mal Loye hit 30 but he became Harmison's fourth victim, Gordon Muchall taking a catch at third slip.
Flintoff, eager to get some time in the middle on his latest return from injury, was out for a five-ball duck when he was brilliantly caught by Claydon off the bowling of Onions.
Harmison completed his first five-wicket haul of the season when Glen Chapple edged a drive to Michael Di Venuto at second slip and Onions and Blackwell wrapped up the win with the final three wickets.
Reaction from BBC Newcastle's cricket reporter Martin Emmerson:
It was hard to make runs out there, but while Lancashire's players celebrated on day one after taking quick wickets I always had the feeling they were going to have to face the backlash from a hardy Durham attack.
As for the watching England selector James Whitaker, who would he hand the new ball to?
Graham Onions and Steve Harmison blazed the trail for Durham. Harmison's treatment of Francois du Plessis on the final morning is something the batsman won't forget in a hurry. And the seamer took another five-for into the bargain.
Saj Mahmood's career best 6-30 for Lancs is also the best return for a bowler in Division One this season. He was assisted by Andrew Flintoff and Glenn Chapple who also bowled well, but they ended up on the losing side because Durham had that little extra resolve thanks to Ian Blackwell and his 74 in the second innings.
Over the three days that was probably the defining moment of a low scoring epic.
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