The original county seat was Puerto De Luna, but was moved north to Santa Rosa in 1903.

That same year, after the popular Spanish–American War of 1898, the county's name was changed to Leonard Wood County after the Presidential physician, Major-General in the Rough Riders, and recipient of the Medal of Honor.

[3] The County contains whole, or parts of, several previous Spanish land grants to include the Aqua Negra, the Jose Perea, the Anton Chico, and the Preston Beck land grants.

[5] As of the 2000 census,[11] there were 4,680 people, 1,655 households, and 1,145 families living in the county.

The racial makeup of the county was 54.1% White, 1.3% Black or African American, 1.1% Native American, 0.5% Asian, nil% Pacific Islander, 39.1% from other races, and 3.6% from two or more races.

27.9% of all households were made up of individuals, and 11.5% had someone living alone who was 65 years of age or older.

As of the 2010 census, there were 4,687 people, 1,766 households, and 1,114 families living in the county.

In 2024, however, Guadalupe County saw a trend toward the Republican Party in line with majority-Hispanic counties nationally when Donald Trump came within less than 1% of flipping it, with Kamala Harris holding it by a plurality and winning by only 14 votes.