La Mesa lies directly to the east of the City of San Diego.  The area was part of the Mission San Diego de Alcala and then, in 1821, was granted as a rancho to Santiago Arguello. Robert Allison bought 4,000 acres from Arguello in 1868. His ranch and rest stop were known as Allison Springs. The area boomed along with the rest of San Diego in the 1880s when water and rail transportation became available. 

Allison and A.S. Crowder filed the La Mesa Springs subdivision map in 1894. The new town grew when Ed Fletcher and William Gross established an artist's community on the eastern edge of town. Grossmont, a mountain residential area named for Gross, boasted residents such as Owen Wister, author of the Virginian, and several famous performers. In the mid-1920s, Mt. Helix was developed as a residential and avocado growing area.

La Mesa has worked hard to maintain its friendly neighborhoods and its position as a major retail area serving East County. The city is currently working to rehabilitate aging commercial areas into strong mixed use developments. 

The Downtown Rebound program is working to rezone areas along El Cajon Boulevard, University Avenue and La Mesa Boulevard in order to facilitate new developments that will include apartments and condominiums as well as small scale retail and service businesses. According to Dave Witt, community development director, interest in the areas is high and there are already developers who want to work in the area. Beautification of El Cajon Boulevard began in 2001 and includes planting, irrigation, accent lighting and modifications to curbs.  The median landscaping includes improvements that will improve traffic safety.