Historically, Calimesa began as a small rural town with mostly single-family homes and ranches.

With completion of U.S. Route 99 (modern day I-10), businesses opened and Calimesa began to take on a separate identity from the larger neighboring town of Yucaipa.

In June 1929, nearly 100 residents attended a meeting and decided to apply for their own post office and to start a “name contest” in which the winner was paid $10.

Calimesa was chosen from 107 names submitted, and is said to come from “cali” (referring to California) and “mesa” from the Spanish word meaning "table" or "table-lands."

The need for a land route to these missions inspired Captain Juan Bautista de Anza to lead a party through the area in 1774.

[6] A site within the rancheria, the location of the present Highland Springs Ranch & Inn, along with Whitewater, and a house at the east end of present-day Singleton Road in Calimesa, all became stage stops along this path.

Volunteers built a community center at the corner of Bryant and Avenue H, which had been designated a park site by the Redlands-Yucaipa Land Company.

The "South Mesa Water Company" purchased the land for a well site and allowed the association to use it for community events.

The Improvement Association and the Chamber have operated as a mix of promoting Calimesa, providing community service, and being a sounding board for residents’ problems.

Prior to 1949, the fire protection for the valley was provided by the California Department of Forestry at the Avenue A station, which today is the office of County Service Area 63 in Yucaipa.

Calimesa community members felt the need for more protection on the south side of the wash, so in 1949 they formed the Volunteer Fire Department.

Prior to its incorporation, the City of Calimesa existed as an unincorporated census designated town that straddled the Riverside–San Bernardino County line at the location where Interstate 10 climbs the San Gorgonio Pass going eastward from Redlands, California.

Calimesa is located in the region known as the Inland Empire, which covers San Bernardino and Riverside Counties.

Situated within the foothills of the San Bernardino Mountains, the city's elevation ranges between 2,300 to 3,500 feet (700 to 1,070 m) above sea level.

According to the United States Census Bureau, the city has a total area of 14.8 square miles (38 km2), all of it land.

According to the 2010 United States Census, Calimesa had a median household income of $44,817, with 14.5% of the population living below the federal poverty line.

Calimesa's only currently-operating elementary school—and only currently operating high school—is Mesa Grande Academy, a private K-12 school owned by the Seventh-day Adventist Church.

Police services in Calimesa are provided by the Riverside County Sheriff's Department via the Cabazon regional station.

Although there are several clinics in Calimesa, the nearest medical facilities are in Yucaipa, Redlands, Banning and Beaumont.