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The natural boundary that extends along a large portion of the United States border with Mexico is the Rio Grande. This separates Mexico and Texas.  Elsewhere to the west, there is no natural boundary except the Colorado River for a relatively short stretch.

Explanation:

The Rio Grande runs along 1,254 miles of the border between Texas and Mexico,  but west of the city of El Paso there is no natural geographic barrier except for a small stretch of the Colorado River in Arizona and California. The Colorado River forms the border with Mexico for a relatively short distance of 17 miles, between Baja California and Arizona.  The river runs along the border between Mexico and Arizona until it reaches Luis Rio Colorado where the river crosses into Mexico entirely. The dams and diversions the United States has built have made this part of Mexico much arider than it was in the past. There were marshlands in the river delta before the United States started diverting water at various points into California and Arizona to favor agricultural development.