Antonio Briseno scored with Mexico's first shot on goal in the 31st minute, and Giovani Casillas added the clincher in the second-minute of injury time to give Mexico a seventh straight victory at the biennial youth championship by a combined score of 17-7.
Briseno scored the only goal Mexico needed when the Atlas defender finished a play that started with Kevin Escamilla chasing down an attempted clearance of a corner kick and curled a ball to the back post. Carlos Fierro headed the ball back into the center of the area and Briseno, pushed forward on the set piece, was able to volley it from just inside the six.
Casillas tacked on a celebratory tally to the delight of the capacity crowd at Estadio Azteca, taking a ball from Arturo Gonzalez on the counter as Uruguay was pushed forward, racing past defender Alejandro Furia and unleashing a shot that keeper Jonathan Cubero was able to get a hand to, but not stop.
The title comes two weeks after the senior Mexican team won the CONCACAF Gold Cup in Pasadena, California, and adds to the U-17 crown won in Peru in 2005.
Uruguay was hampered early, losing forward Rodrigo Aguirre in the 23rd minute to an injury when he and Mexican keeper clashed heads going for the same high bouncing ball just outside the penalty area.
Aguirre had to be removed from the field on a stretcher and reportedly was taken to a hospital for examination.
With Juan San Martin replacing Aguirre, Uruguay created chances quickly, countering three-on-two but wasting the chance when Elbio Alvarez put the shot well wide right in the 26th minute.
Buoyed by the sellout home crowd, Mexico enjoyed most of the possession and outshot Uruguay 23-15. But Uruguay had more shots on goal, including twice hitting the post, by Alvarez in the 35th and again with San Martin's left-footed attempt from the edge of the six in the 62nd minute.