Ntamack broke through several tackles as he raced 65 yards to score the winning try, a moment of excellence to cap off a high-quality final that see-sawed one way and then the other.
Toulouse extended their record number of Top 14 wins to 22 and denied La Rochelle their first. Centre Santiago Chocobares also crossed for a try in the opening half as the teams went to the break at 13-13.
Scrumhalf Tawera Kerr-Barlow and prop Uini Atonio scored tries for La Rochelle, who trailed by 10 points in the opening period, then rallied to lead going into the closing stages, but could not hold on for the win.
Fullback Thomas Ramos kicked 19 points for Toulouse as they matched La Rochelle’s physicality and had the guile to get them over the line and deny the latter a maiden domestic title to go with their recent European success.
"We almost did not believe we could do it at the end, and then there is a stroke of genius from Romain," Toulouse's Julien Marchand told France 2.
"We were undisciplined and almost paid for it. But congratulations again to them (La Rochelle) because they were very, very strong, and they had a very good season."
Toulouse scored their first try thanks to another excellent solo effort from Chocobares, who profited from a La Rochelle fumble near the halfway line to race clear and score in the corner.
La Rochelle levelled just before halftime through Kerr-Barlow, and score again early in the second period when Atonio crossed the line.
The unerring boot of Thomas Ramos put Toulouse back in front just past the hour-mark as he landed three penalties to give them a 22-20 advantage, but that seemed to spur La Rochelle back into action.
They forced two penalties that were kicked by Antoine Hastoy, part of a haul of 16 points for the flyhalf, but Ntamack had the final say.
"It's hard," Hastoy said. "We executed our plan for 77 minutes. And then you have it, a lack of connection in our defence. It's hard to see scenes of joy on the other side."
