- Ludovic Blas (75' Pen)
- Logan Costa (4', 10')
- Thijs Dallinga (23', 31')
- Zakaria Aboukhlal (79')
Nantes had won consecutive finals in 1999 and 2000.
Toulouse's only previous trophies came from winning Ligue 2 on three occasions, the last time in 2021-22.
The French Cup triumph also secured Toulouse a place in the Europa League, their first European competition since 2009-10.
Toulouse went ahead in the fourth minute through Costa and he doubled their lead six minutes later with another header.
Toulouse, beaten 3-1 by Nantes in their only league clash so far this season, were soon three goals in front after Gabriel Suazo teed up Dallinga by supplying a stunning cross into the box for the Dutchman to score with a chipped finish.
Dallinga then made it 4-0 just after the half-hour mark when he netted from close range from a rebound.
Nantes, who are without a Ligue 1 win since mid-February and have yet to secure their top-flight status for next season, made three half-time changes, introducing forwards Andy Delort and Ignatius Ganago with midfielder Samuel Moutoussamy.
They managed to pull a goal back with a penalty as midfielder Ludovic Blas fired into the roof of the net 15 minutes from time but Toulouse's Aboukhlal wrapped up a one-sided victory by smashing home their fifth from distance.
Nantes, who are only outside the relegation zone on goal difference, had a fine run to the final having beaten Lens 2-1 in the quarterfinals and Lyon 1-0 in the semis.
Toulouse, 12th in the French top tier, beat Ligue 2 sides Rodez and Annecy in the quarters and last four respectively.
- Benoit Millot