Long-known as a Seventh Day Adventist community, Loma Linda was not officially incorporated until 1970. However, the city's history stretches well back into the mid-1800s as part of the early settlement of Rancho San Bernardino.

In the mid 1880s, a large portion of land was purchased for development by a Riverside investor group. The Mound City Land and Water Company began plotting 200 acres for citrus, residential and a few small shops. The new development was named "Mound City" noting its slightly higher elevation relative to the surrounding area.

By 1887, the investment group opened a hotel and health resort named the Mound City Hotel. However, an untimely drought and competition from other nearby resorts doomed the hotel.

In the late 1890s, the hotel was purchased by a group of Los Angeles physicians and businessmen. The resort was remodeled and cottages were added. The newly christened resort was renamed "Loma Linda" (Spanish for "pretty hill"). By 1904, however, the hotel and resort was once again out of business.

The very next year, the Loma Linda resort came to the attention of a prominent Seventh Day Adventists named Ellen G. White, who wanted to establish a West Coast medical college for the church. Nursing instruction began soon thereafter and by 1910, Loma Linda Medical College officially opened its doors, graduating its first class four years later.

Loma Linda Medical College is now known as Loma Linda University. Its adjacent medical center (Loma Linda University Medical Center - LLUMC) is one of the top pioneering medicine centers in the United States. The medical center's 11-story facility opened in 1967.

In 1990, LLUMC opened the world’s first hospital based proton cancer treatment center. In 1993, a children's hospital was added and in 1996 a Ronald McDonald Children's House was built nearby.

In 1977, the Jerry L. Pettis Memorial VA Medical Center opened. Named after Congressman Jerry L. Pettis, a World War II veteran who secured funding for its construction, the facility serves veterans residing within the two-county region.

Today, Loma Linda remains dominated by the University and associated medical community, however, with only 20,000 residents, the town retains its small-town atmosphere.