The Mexicans opened the scoring on 31 minutes through Antonio Briseno and held onto the smallest of margins until Giovani Casillas' second-half stoppage-time goal, which triggered the celebrations.
The triumph was Mexico's second Under-17 world crown, following on from their victory in Peru in 2005.
Mexico also won the Gold Cup last month in senior football, continuing a rich period for football in the North American nation.
The host nation got the opener after top scorer Carlos Fierro flicked on a cross from the right for Briseno to volley home.
Uruguay had their chances to level with Elbio Alvarez hitting the crossbar, but in their bid for an equaliser Mexico hit them on the counterattack in stoppage-time through Casillas.