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Mesilla, also known as La Mesilla or Old Mesilla, is an incorporated town in Dona Ana County, New Mexico, in the Las Cruces metropolitan area.

The first permanent settlement in Mesilla was established in the 1840s by 116 settlers from Chihuahua led by Pablo Melendres.

The village of Mesilla was incorporated in 1848, after the Treaty of Guadalupe Hidalgo moved the United States-Mexico border south of the village of Dona Ana, and the boundary dispute over the Mesilla Valley was finally resolved by the Gadsden Purchase of 1853.

During the Civil War, Mesilla served in 1861 and 1862 as the capital of the Confederate Territory of Arizona.

Mesilla stood at the crossroads of two major stagecoach, mail and trade routes, the Butterfield Overland Mail and the Camino Real de Tierra Adentro, and in its heyday, with about 2,000 residents, it was the largest city between San Antonio and San Diego.

In 1881 the Santa Fe Railway bypassed Mesilla in favor of nearby Las Cruces after Mesilla's landowners asked too much for right-of-way land and a Las Cruces landowner offered land free; Mesilla has grown little since, while Las Cruces became New Mexico's second-largest city.

An 1871 riot in Mesilla between supporters of rival congressional candidates Jose Francisco Chaves and Jose Manuel Gallegos left nine men dead and nearly 50 injured, the worst political riot in New Mexican history.

The La Mesilla Historic District, which includes Mesilla Plaza, was declared a National Historic Landmark in 1961, and the plaza's Fountain Theatre has been in operation since the early 1900s, except for a closure of 12 years.

The Basilica of San Albino, the Roman Catholic parish church standing on Mesilla Plaza, was raised to the status of a minor basilica by the Holy See in 2008.

The 2020 census counted 1,797 residents in Mesilla, down 18.2 percent from 2,196 in the 2010 census.