For Leinster this agonising reverse in London meant they have lost the last three Champions Cup finals following successive defeats by another French club, La Rochelle.
Superb defence was behind Toulouse's victory as they gained revenge for 2022 and 2023 semi-final defeats by Leinster.
Neither side managed a try in a regulation 80 minutes at the Tottenham Hotspur Stadium that ended level at 15-15 after five penalties apiece
Leinster, however, had arguably had more and better chances.
Toulouse then struck early in the first 10 minutes of extra time with a try from wing Matthis Lebel.
But they had to play the bulk of the additional 20 minutes a man down after Richie Arnold was sent off before penalties from fellow replacement Thomas Ramos proved decisive.
"It is awesome to be able to win with this team," Toulouse captain Antoine Dupont, the player of the match, told ITV 4.
"We really wanted to win the sixth star after losing to Leinster over the last two years," the France scrum-half added.
For Lebel, victory took some off the edge of France's failure to win last year's World Cup on home soil.
"When one has worked for a long time together to win this, this sparks a lot of emotion," said Lebel after Toulouse's first Champions Cup final win since 2021.
"Everyone remained focused on this as a target despite the disappointment of the World Cup."
'Devastated'
Leinster boss Leo Cullen admitted: "We had plenty of opportunities...We're devastated we couldn't get over the line.
He added: "Toulouse were probably just a bit more clinical."
Leinster wing James Lowe had just been sin-binned for a deliberate knock-on and the Dublin-based team were effectively two men down, with replacement Ciaran Frawley injured, when Lebel sprinted in for the first try of the match.
Ramos converted and then added a penalty to make it 25-15.
But in a further twist, Arnold was red-carded by English referee Matthew Carley in the 89th minute for an illegal clear-out on Cian Healy.
Leinster eventually scored a try when Josh van der Flier burrowed over from close range although it needed a lengthy television review to confirm the grounding.
Frawley converted and Leinster were within three points at 22-25 come the end of the first half of extra time.
But Ramos landed two more penalties as Toulouse pulled nine points clear.
Earlier, Toulouse full-back Blair Kinghorn and Leinster fly-half Ross Byrne each kicked four penalties, before Ramos's long-range effort nudged the Top 14 team three points ahead in the 70th minute.
Leinster, themselves four-time champions of Europe, equalised with a penalty from Frawley who was then off target with a last-minute drop-goal that would have won the game.
"I'm absolutely exhausted, the boys put in a hell of a shift," said Kinghorn. "It's unbelievable, I'm lost for words. The boys dug in so deep and that second half of extra-time was enormous from us."
Saturday's match was the first time the European heavyweights had met in a Champions Cup final.
Scotland full-back Kinghorn, preferred to Ramos, kicked Toulouse into a 6-0 lead.
Leinster, rather than go for goal with a penalty, kicked for an attacking line-out near Toulouse's line in the hope of scoring a try.
But, as happened several times, brilliant Toulouse defence kept Leinster at bay.
Kinghorn's third successful goal-kick made it 9-3 before he was just short with a difficult 45-metre penalty and Byrne made it 9-6 at the break.
