Final answer:
The Mexican-American War and the subsequent Treaty of Guadalupe Hidalgo enabled the United States to acquire over 500,000 square miles of land, furthering Manifest Destiny and significantly increasing its territory through strategic acquisitions such as the Gadsden Purchase.
Step-by-step explanation:
The conflict that helped the United States acquire more than 500,000 square miles of land was the Mexican-American War, concluded by the Treaty of Guadalupe Hidalgo. This treaty confirmed the U.S. title to Texas and ceded the Alta California and New Mexico territories to the United States. As a result, Mexico lost over half of its territorial landmass, which eventually comprised all or parts of states such as California, Arizona, New Mexico, Texas, Utah, Nevada, Colorado, Wyoming, and Kansas. This further entrenched the concept of Manifest Destiny, a belief that the expansion of the United States across the North American continent was both justified and inevitable.
Following this, the Gadsden Purchase of 1854 finalized the present border between the United States and Mexico with the acquisition of Arizona's Mesilla Valley. This acquisition was not only a strategic move for the construction of a southern transcontinental railroad but also the last major territorial expansion in the continental United States. These acquisitions signified a tremendous increase in U.S. landholdings and played a critical role in the country's development and resource exploitation.