Doña Ana is a Democratic-leaning county in Presidential and Congressional elections. Since 1920, Doña Ana has voted for the candidate who also won statewide, the only exception being in 2004 when Democrat John Kerry won Doña Ana 51–48%, while Republican George W. Bush won statewide 50–49%. The last Republican to win a majority in the county was George H. W. Bush in 1988. In 2008, Democrat Barack Obama won 58% of the county's vote. In 2016, Republican Donald Trump won 35.9% of the county's vote, the lowest share for a Republican candidate since 1936.

Doña Ana is part of New Mexico's 2nd congressional district, which is held by Republican Stella Yvette Herrell. In the State Senate Doña Ana is part of the 31st, 36th, 37th, 38th, and 40th Senate districts, which are held by Democrats Joseph Cervantes, Jeff Steinborn, David Soules, Mary Kay Papen, and Republican Bill Burt, respectively. In the State House Doña Ana is part of the 33rd, 34th, 35th, and 52nd House districts, which are held by Democrats Bill McCamley, Bealquin Gomez, Angelica Rubio, and Joanne Ferrary, respectively, the 37th and 53rd House districts, which are held by Republican Ricky Little, respectively, and the 36th House district, which is held by Nathan Small. Current County Commissioners are as follows: Lynn Ellins (District 1), Ramon S. Gonzalez (District 2), Shannon Reynolds (District 3), Isabella Solis (District 4), and VACANT (District 5).