The airport first opened in 1941 as a military airfield as the United States entered into World War II. After the war, the airport was sold to the city and all commercial activity was moved from the former Santa Fe Municipal Airport/Boyd Field, which was located off Cerrillos Road between Rodeo Road and Jaguar Drive. The new airport was called the Santa Fe County Municipal Airport until 2018, when the name was changed to Santa Fe Regional Airport. The current terminal building was opened in 1957 and has 11,000 square feet of space. It was renovated in 1988 and again in 2004 and has seen a major expansion starting in 2022. In June 1972, Frontier and Texas International Airlines, the two local service air carriers serving Santa Fe, abruptly ended service, citing unsafe runway conditions after multiple aircraft received prop damage from deteriorating asphalt. Neither carrier ever returned, and the airport then began receiving service by commuter airlines operating much smaller aircraft. In 1983, Santa Fe saw its first code share service by a commuter airline on behalf of a major airline. Smaller 19-seat aircraft were mostly used, with the exception of a brief period in 1997 and 1998, when Santa Fe saw two carriers using 32-seat aircraft.

The airport lost all airline service at the end of 2007 but resumed service in the summer of 2009, when it gained its first major airline code share flights using regional jets. Passenger traffic responded tremendously to the new jet service, and regional jet flights increased from once per day in 2009 to as many as twelve per day in 2019.

To help with the increase in passenger traffic, the terminal was remodeled in 2016 by removing much of the restaurant for added gate space. The airport manager's office was converted to a baggage claim room, while the manager was relocated to a portable building. Aircraft had been parked parallel to the terminal building, accommodating a maximum of two regional jets, but were changed to park head in so that three aircraft could be accommodated. On September 27, 2017, the Santa Fe City Council approved an expansion plan for the airport to better accommodate the current volume of airline service as well as future growth. This includes expanding the terminal with added gate space, a new addition for the baggage claim area and rental cars, and a new parking lot with 750 spaces. Coinciding with the approval of this expansion plan was a renaming of the airport from Santa Fe Municipal Airport to Santa Fe Regional Airport. Funding and planning for the expansion began in 2019. A design was completed by Molzen Corbin in 2021, and the only bid received was by Bradbury Stamm Construction. Work began on February 25, 2022 and was expected to take 12–14 months. The expansion incurred several major delays but was completed in April, 2024, 26 months after work began. The expansion included a 7500 ft addition to the north side of the terminal as well as remodeling of the entire terminal. The parking area was completely rebuilt with the addition of three new long-term lots. The roadway alignment in front of the terminal was redesigned and opened in July, 2024. A second phase of terminal expansion is planned for a 13000 ft addition to the south side of the terminal which will include a new departure gate area and a restaurant. The recently completed addition currently housing a new gate area will be converted to baggage claim. Until then, baggage claim is in a portable building. An extension of Jaguar Road from NM 599 (the Santa Fe Bypass) exit #2 directly to the terminal is also planned for the future.

Historical airline service

Santa Fe's first commercial airline service was by Mid Continent Air Express beginning in 1929 operating on a route from El Paso to Denver with stops at Albuquerque, New Mexico, Santa Fe and Las Vegas, New Mexico as well as Pueblo and Colorado Springs, Colorado. The route was replaced with Western Air Express in 1931 and again by Varney Speed Lines, the predecessor of Continental Airlines, in 1934. The southwest division of Varney was operating daily round trip air service flown with a single engine Lockheed Vega aircraft on a routing of El Paso - Albuquerque - Santa Fe - Las Vegas, NM - Pueblo, CO with continuing service operated by Wyoming Air Service on to Colorado Springs, Denver, and Cheyenne, WY. In 1936, the southwest operating division of Varney was acquired by Robert F. Six who in 1937 renamed the air carrier Continental Air Lines which then began operating Lockheed Model 12 Electra Junior twin prop aircraft on a daily round trip routing of El Paso - Albuquerque - Santa Fe - Las Vegas, NM - Pueblo, CO - Colorado Springs - Denver. Mr. Six would serve as CEO of the airline until 1981. Thus, Santa Fe was one of the first destinations served by Continental which would become a major domestic and international airline. In 1940, Continental began operating Lockheed Model 18 Lodestar twin prop aircraft and extended single plane service from Santa Fe and Albuquerque to Roswell and Hobbs, New Mexico as well as Midland/Odessa, Big Spring, San Angelo, and San Antonio, Texas.