One conflict that immediately comes to mind is the "Guerra de Castas" in the Yucatán peninsula, it might've started as a small conflict, but it ended up lasting over 50 years and changing the history of Mexico.

During the start of the conflict Yucatán was an independent republic (1847) that had successfully defeated Mexico in open warfare with the help of the Maya people that were now armed and that refused to return the weapons. When in the hopes of stomping an incoming revolt the governor of Yucatan ordered the execution of one of the Maya leaders (Manuel Antonio Ay) in Valladolid.

The response of the Maya leaders was swift and sanguinary, every white person of the town of Tepich was executed, the same happened on a number of towns where the white population was killed by the rebels. By 1848 only Merida and Campeche (that were walled cities) and some coastal towns were not controlled by the rebels, the government started asking for support to a number of powers in exchange of joining them, offers were made to the United States, to the British and to the Spanish but everyone declined. Mexico agreed to lend its support in exchange of reincorporation to the Mexican republic. This support, combined with the partial retreat of the rebel armies for the harvest season made posible to capture most of the rebel held territory. By 1850 the mayas had retreated to what became Chan Santa Cruz where they established their nation and kept using guerrilla warfare for more than 5 decades. The last 2 bastions of the rebels, Chan Santa Cruz and Bacalar did not fall until 1901, when Mexican federal troops finally occupied them.