While Juventus collapsed in the first leg to draw 2-2, it was Tottenham's turn at Wembley Stadium to throw away a winning position and go out with a 4-3 aggregate loss.
When Son Heung-min capped a dominant first half for Tottenham with a goal, it should have been a platform to build on for a team without a domestic league title in 57 years against one that's won the last six Serie A titles.
And it was pair of Argentines that ended the hopes of compatriot Mauricio Pochettino, the Tottenham manager.
Higuain struck from close range in the 64th minute and then created the winner, holding off three Tottenham players before feeding Dybala to net his first Champions League goal of the season.
More From This Section
From a position of strength, this was a capitulation stemming from a loss of concentration and composure by the hosts.
"I think we conceded three chances and they scored twice," Pochettino said.
There was one chance to force the game into extra time in the 90th. Harry Kane's header hit the post and the ball crept across Gianluigi Buffon's goal line before being hooked clear by Andrea Barzagli.
"It's the history of Tottenham," Juventus defender Giorgio Chiellini said.
"They always create many chances to score ... but at the end they miss something."
For Tottenham, which beat holder Real Madrid and Borussia Dortmund in the group stage, there would be no third European Cup quarterfinal in its history. Instead Pochettino's side became the first English side to be eliminated in the Champions League this season.
A day after Liverpool ousted Porto, Manchester City advanced Wednesday with a 5-2 victory over Basel despite losing 2-1 at the Etihad Stadium.
Unlike City, Spurs lacked a comfortable lead to be so relaxed. But they had chances to build one early in the second leg.
Son forced an early save out of Buffon and Kane broke past Chiellini and rounded the goalkeeper only to hit the side netting.
When Tottenham rues its second-half collapse, it should remember how fortunate it was to avoid losing a player and conceding a penalty in the 17th minute when Douglas Costa was tripped by Jan Vertonghen.
Christian Eriksen slipped the ball through to Alli but Andrea Barzagli intervened with a sliding tackle. The ball reached Kieran Tripper on the right and a cross was whipped in for Son, whose scuffed shot found its way into the net.
For a player used to yielding the spotlight to Kane, Son is emerging as a similarly potent force in the team with five goals in his last three goals -- 16 in all competitions this season.
But Juventus was not going to go down without a fight.
Then came the double substitution around the hour mark that turned the game in Juve's favour.
Kwadwo Asamoah came on for Blaise Matuidi, while Stephan Lichtsteiner replaced Medhi Benatia. And it was Lichtsteiner's cross that Sami Khedira headed on to Higuain at the far post to reduce the deficit.
Before Tottenham could regroup it was trailing after Dybala raced onto Higuain's pass and lifted the ball over goalkeeper Hugo Lloris.
"We said, 'Keep calm and the chances surely would arrive,'" Chiellini said.
While Juventus now chase a third appearance in a final in four seasons, Tottenham try to hold on to their top-four position in the Premier League to secure their return to the competition next season.