In a game played to the backdrop of non-stop whistles and jeers by Morocco's passionate fans, the team relied almost exclusively on counterattacks and scored from one of them.
A cross was swung in from the left and En-Nesyri leapt between Portugal goalkeeper Diogo Costa and defender Ruben Dias to head into the empty net.
Ronaldo, who will be 41 by the time of the 2026 World Cup in the United States, Mexico and Canada, had been looking to reach the semifinals for only the second time after 2006.
Try as he might, he barely got a touch of the ball until stoppage time when he got in behind Morocco's defense off a long ball forward. His low shot was saved by goalkeeper Yassine Bounou, who hadn't had too much to do before that point.
Substitute Walid Cheddira was shown a red card for Morocco in stoppage time for collecting a second yellow card in as many minutes. Portugal center back Pepe then headed wide from inside the six-yard box.
Ronaldo fell to his knees in dejection. While Lionel Messi will be in the semifinals with Argentina, the other soccer great of this generation won't be.