[6] Prior to European settlement, Mira Mesa was inhabited by the Kumeyaay peoples who lived along Penasquitos Creek.

[citation needed] Starting in 1969 there was a housing boom in the area that now extends from the I-15 freeway in the east to I-805 in the west and is approximately 10,500 acres (42 km2).

Mira Mesa was the northernmost "real community" of San Diego, and was separated from the rest of the city by NAS Miramar for many years.

[9] By the late-1990s, the Mira Mesa area had undergone extensive expansion to accommodate the thousands of new residents attracted by its proximity to major employers like the University of California, San Diego, Marine Corps Air Station Miramar, Qualcomm, and dozens of biotech and pharmaceutical companies.

Fire Station #38, which includes Engine 38, Truck 38, and Paramedic 38, is located on New Salem Street near the main Mira Mesa Park and Recreation Center.

A police storefront located adjacent to the Epicentre along Mira Mesa Boulevard serves the local area including Scripps Ranch.