Centre-back Logan Costa and striker Thijs Dallinga both struck braces for Philippe Montanier's side during a first-half demolition job, all but ending the match as a contest before the break.
Ludovic Blas pulled one back from the spot as the game entered its final 15 minutes, but Zakaria Aboukhlal restored Toulouse's four-goal advantage soon after, as Nantes ceded their crown with a whimper.
Amid their scrap for survival in Ligue 1, Nantes had established a reputation as knockout specialists for the second season running with victories over Lens and Lyon en route to this year's Coupe de France final.
However, Antoine Kombouare's men were torn to shreds in a totally one-sided first half, where centre-back Costa took just four minutes to break the deadlock, meeting Branco van den Boomen's corner to fire a header into the net.
Sparingly used in Ligue 1 this season, Costa had been an ever-present for Toulouse in the cup, and the Cape Verde international more than repaid Montanier's faith in him with an unforeseen double after just 10 minutes.
A free kick from the right was whipped in by Van den Boomen and subsequently missed everyone, but Stijn Spierings kept the ball alive for Costa to nod home unchallenged.
Costa had already become the unlikeliest of heroes for Les Violets, but marksman Dallinga soon wanted his own slice of the action and put the result beyond any doubt in the 23rd minute, latching onto Gabriel Suazo's inch-perfect pass and delicately lifting the ball over Alban Lafont.
Dallinga took just another eight minutes to join Costa in the two-goals club, although he was helped by some questionable goalkeeping by Lafont, who parried Fares Chaibi's effort straight into the Dutchman's path for a simple tap-in.
A mortified Kombouare made a triple substitution at half time, introducing both Ignatius Ganago and Andy Delort up top as well as Samuel Moutoussamy in midfield in a desperate attempt to spark an astonishing comeback.
However, Nantes had seemingly consigned themselves to their fate and showed little signs of a revival in the second half, although Moussa Sissoko wasted a golden chance for a consolation in the 56th minute, blazing a volley over the bar after Toulouse goalkeeper Kjetil Haug came for a corner and missed.
The Canaris faithful had something to cheer in the 75th minute, though, as Blas crashed a penalty down the centre of the goal, but Toulouse quickly responded just three minutes later.
A low Van den Boomen free kick caused chaos in the Nantes area, and a weak attempt at a clearance fell at the feet of Aboukhlal, who drilled a first-time strike into the top corner from the edge of the box.
By clinching France's premier cup honour for the first time in their 53-year history, Toulouse would qualify for next year's Europa League group stage in normal circumstances, but the Violets' ownership situation could cause a problem in that regard.
Both Toulouse and Italian powerhouses AC Milan are owned by RedBird Capital, and UEFA regulations prohibit two teams under the same ownership competing in the same tournament, which would also apply if Milan dropped down from the Champions League into the Europa League.
Attention now turns back to Ligue 1 for both sides, as 12th-placed Toulouse aim to take another step towards confirming their safety when they face Lens on Tuesday, while 16th-placed Nantes continue their fight against the drop away to fellow relegation candidates Brest on Wednesday.