In 1632, a short-lived mission of Franciscans under Spanish auspices was founded in the area to serve native people.

The settler Bartholomew J. DeWitt founded the village of Santa Angela outside the fort at the junction of the North and South Concho Rivers.

The town became a trade center for farmers and settlers in the area, as well as a fairly lawless cowtown filled with brothels, saloons, and gambling houses.

After being designated as the county seat, the town grew quickly in the 1880s, aided by being on the route of newly constructed railroads.

The Santa Fe Railroad arrived in 1888 and the Kansas City, Mexico and Orient Railway in 1909.

[11] After a tuberculosis (TB) outbreak hit the United States in the early 1900s, many patients moved to San Angelo.

TB sufferers went to San Angelo for treatment, and a sanitarium was built in nearby Carlsbad.

In 1928, the city founded San Angelo College, one of the region's first institutes of higher education.

The military returned to San Angelo during World War II with the founding of Goodfellow Air Force Base, which was assigned to train pilots at the time.

[13] San Angelo was famous for Miss Wool of America Pageant, an annual event organized by the National Wool Growers Association (U.S.)[14] According to the United States Census Bureau, the city has a total area of 58.2 sq mi (150.9 km2), of which 2.3 sq mi (6.1 km2) (4.03%) are covered by water.

[27] In 2009, CNN Money ranked San Angelo as one of the best cities to launch a small business.

[29] Although most oil fields lie to the west, many oil-field service companies based in the city employ a large number of local residents.

San Angelo serves as the regional medical center for west-central Texas.

Shannon Medical Center employs over 3,000 in San Angelo[30] and provides services to a large region of west-central Texas.

[34] The several large institutional employers in the city include Shannon Medical Center, Angelo State University, and Goodfellow Air Force Base.

[35] The San Angelo Performing Arts Center (PAC) provides access to the highest level of performing arts by presenting local, national, and international touring shows at two historic venues: the 1,350-seat 1928 Murphey Auditorium and the Stephens Performing Arts Center (formerly a Coca-Cola factory) which contains the 300-seat Brooks and Bates Theater, a black-box theater, seven ballet studios, and administrative spaces.

These concerts take place the first Saturday of October, November, December and February in the Murphey Performance Hall.

Though wavering economic times and two world wars stopped artistic efforts in the community on a number of occasions, theatrical productions continued.

Ballet San Angelo was founded in 1983 for the purpose of presenting an annual production of The Nutcracker.

It offers a full season of productions including a choreography performance and a Children's Ballet.

[42] Angelo State University, through "The Arts at ASU", puts on six plays a year open to the general public.

Many activities are available within the park, including camping, picnicking, and swimming, as well as hiking, mountain biking, orienteering, and horseback riding on over 50 miles (80 km) of developed trails.

[48] The center includes the Spring Creek Wetland, which has 260 acres (110 ha) being developed by the Federal Bureau of Reclamation, including a 7-mile (11 km) trail; its terrain varies from a semiarid environment to a freshwater marsh.

[49] Historic Fort Concho, a National Historic Landmark maintained by the city of San Angelo, was founded in 1867 by the United States Army to protect settlers and maintain vital trade routes.

[53] It includes a parade, carnival, and concerts, and many other events in addition to the main stock show and rodeo.

[55] The university is divided into six colleges: Business, Education, Liberal and Fine Arts, Nursing and Allied Health, Sciences, and Graduate Studies.

[56][57] San Angelo has a branch of Howard College, which is based in Big Spring, Texas.

The two-year school prepares students academically for transfer to a four-year university, and concentrates in technical and occupational fields of study that lead to certificates and/or associate in applied science degrees.

The Goodfellow Campus Center has been providing higher education to the Concho Valley area since 1989.

[63] The BNSF Railway serves the town and the Texas Pacifico has a lease on a TxDOT owned rail line.