Santa Rosa is a town, and the county seat of Guadalupe County, New Mexico. The population was 2,744 at the 2000 census. It is a small town between Albuquerque and Tucumcari, situated on the Pecos River at the intersection of I-40 and Route 54. The town is in the llano estacado or "staked plains" of northern New Mexico.

The first European settlement in the area was Aqua Negra Chiquita, "Little Black Water" in Spanish, in 1865. The name was changed in 1890 to Santa Rosa, Spanish for "Holy Rose", referring to a chapel that Don Celso Baca, the founder of the town, built and named after either his mother Rosa or Saint Rose of Lima. The "Rosa" may also refer to the roses in the story of Our Lady of Guadalupe and is indicative of the Catholicism of the Spanish colonizers who settled in the area.

Santa Rosa was connected by railroad to Chicago, El Paso and the world at large in the early 1900's.

Santa Rosa's stretch of Route 66 is part of film history. When John Steinbeck's epic novel, The Grapes of Wrath, was made into a movie, director John Ford used Santa Rosa for the memorable train scene. Tom Joad (Henry Fonda) watches a freight train steam over the Pecos River railroad bridge, into the sunset.