Mission is in southern Hidalgo County at 26°12′41″N 98°19′17″W / 26°12′41″N 98°19′17″W / 26.21139; -98.32139 (26.211402, -98.321277). It is bordered to the east by McAllen, the largest city in the county, to the north by Palmhurst, to the west by Palmview, and to the south by the Mexico–United States border along the Rio Grande.
The Interstate 2/U.S. Route 83 freeway passes through Mission, south of the center of town. The highway leads east 5 miles (8 km) to downtown McAllen and 41 miles (66 km) to Harlingen. Interstate 2 ends 7 miles (11 km) west of Mission; US 83 leads west 34 miles (55 km) to Rio Grande City.
According to the United States Census Bureau, Mission has a total area of 34.1 square miles (88.2 km2), of which 34.0 square miles (88.0 km2) are land and 0.1 square miles (0.2 km2), or 0.20%, are water.