Exeter struggled with Northampton's physicality at an empty Wembley Stadium and midfielder Ryan Watson put the Cobblers ahead in the 10th minute with a deflected effort following a long throw.
Striker Callum Morton tapped in a second in the 30th minute following a free kick, and a red card for defender Dean Moxey in the second half left Exeter's promotion hopes in tatters.
Two goals in the last 10 minutes from Sam Hoskins and substitute Andy Williams put Exeter to the sword as The Cobblers secured a return to League One after a two year absence.
Story of the match
The teams made just one change between them for the behind closed doors final, with Exeter manager Matt Taylor bringing in Frenchman Nigel Atangana to replace Archie Collins, who played all 120 minutes in the extra-time victory against Colchester.
The unchanged Northampton side unsettled the Exeter defence in the early stages, forcing goalkeeper Jon Maxted into an early error, with the keeper almost slicing a clearance into the path of Northampton striker Vadaine Oliver.
Winger Randall Williams was Exeter's main threat throughout the first half and showed his pace and trickery in the early stages, drawing a yellow card from centre-back Scott Wharton in the third minute before using his pace to get in behind and fire a dangerous ball across the box.
But midfielder Ryan Watson punished a poor clearance in the 10th minute after Exeter failed to clear their lines from a Charlie Goode long throw. The ball found Watson at the edge of the penalty area who sold the onrushing defender a dummy before lashing home through a crowded penalty area via a deflection from Aaron Martin.
Goalkeeper Maxted continued his nervous start, parrying weakly from a Nicky Adams free kick but did enough to get a fist to a bouncing ball with Vadaine Oliver bearing down on goal.
Exeter could not cope with Northampton's dominance in the air, with centre-back Charlie Goode's long throws and Oliver's height causing real problems. And it was a set peice that laid on the second for Callum Morton, who tapped in after a double flick-on from a free kick.
And Northampton would have added a third for half time had it not been for Jon Maxted in the Grecians goal.
The 27-year-old was called into action to tip a Wharton header onto the bar after the centre back rose to meet a free kick, and had to react quickly to push away a powerful header from the resulting corner.
And there was still time before the half time whistle for Northampton to test the overworked Maxted again, with the keeper batting away headers from Oliver and Goode in injury time.
Both teams remained unchanged for the second half, but things picked up from where they'd left off, with Callum Morton laying into the path of Hoskins after good hold up play, only for the midfielder to be dispossesed following a last ditch tackle from Atangana.
Exeter brought on Archie Collins in midfield seemed to get a hold on the game, but a dominance of possession translated into little for the Grecians.
And in the 58th minute Exeter's faint hopes of a comeback heroics were dealt a significant blow as defender Dean Moxey saw red after a full blooded and late lunge on Northampton's Watson.
Next it was Aaron Martin's turn to make a mistake, giving the ball away on the half way line but seeing Morton slot wide of the post after being set free by his striker partner Oliver.
Exeter kept the ball well despite the one man disadvantage, and had claims for a penatly waved away after Mark Marshall nicked the ball off Collins' toe as he wound up for a shot.
But with 10 minutes to go, the team joining Swindon Town, Crewe Alexandra and Plymouth Argyle in League One next season was put beyond doubt.
The energetic Callum Morton chased down a long ball forward and laid the ball off to Marshall. The winger squared the ball into the path of Sam Hoskins who rolled the ball past the keeper to make it 3-0.
And to compound the misery further, two Northampton substitutes combined to add a fourth in the 89th minute.
A Charlie Goode long throw once again caused chaos in the Exeter box, and a flick on by Harry Smith fell into the path of Andy Williams who hooked the ball the home to finish off a dejected Exeter side.
The battering ram that was Northampton was simply too much for Exeter, who simply couldn't handle their opposition from set pieces, with manager Matt Taylor admitting afterwards he'd tried to pick the most physical team possible to counter the Cobblers' approach.
Vadaine Oliver dominated the Exeter centre halves in the air whilst Callum Morton used his athleticism to run the channels and hold up the ball for his team mates.
Northampton's back three never looked in any trouble and we're well protected by their team who dug in at times during the second half.
Northampton's battling approach and danger from set plays will make them hard to beat in League One, and manager Keith Curle will no doubt want to resign on-loan striker Callum Morton for the new campaign.
For Exeter, losing a third play-off final in four years will be tough to take and being bullied tonight will no doubt give the manager something to think about over the summer.
Man of the Match: Callum Morton
A number of Northampton's players rose to the occasion but none more so than the on-loan West Brom striker, who combined perfectly with his strike partner, running the channels, holding the ball up, and capping off his performance with a goal.