What conflict began as a border issue and resulted in significant territorial losses for Mexico?

The Mexican-American War is the correct answer because it directly stemmed from territorial disputes following the annexation of Texas by the United States in 1845. Mexico viewed the annexation as an aggressive act since it had not recognized Texas's independence. The U.S. and Mexico had differing opinions on where the border between Texas and Mexico should be, particularly regarding the Rio Grande and the Nueces River.

As the conflict escalated, the U.S. sought to expand its territory further west, leading to military confrontations. The war officially lasted from 1846 to 1848 and concluded with the Treaty of Guadalupe Hidalgo. This treaty resulted in Mexico relinquishing a massive amount of territory, including present-day California, Nevada, Utah, Arizona, and parts of Colorado and New Mexico.

In contrast, other conflicts mentioned do not primarily focus on border disputes that led to significant territorial losses for Mexico. The Texas Revolution was about Texas independence, the Spanish-American War focused on issues related to Cuba and Puerto Rico, and the Civil War was a domestic conflict within the United States unrelated to territorial negotiations with Mexico. Therefore, the Mexican-American War stands out as the event characterized by border issues leading to substantial territorial changes.