Murrieta takes its name from sheep ranchers Juan and Ezequiel Murrieta, who arrived in Temecula Valley in 1873. That year they formed a partnership with Domingo Pujol (a Spanish born lawyer from San Francisco) and Francisco Sanjurjo and purchased the Rancho Pauba and Rancho Temecula land grants. The partnership ended in 1876 and their holdings divided, with the Murrieta brothers retaining the northern half of Rancho Temecula.

In 1882 the California Southern Railroad, a subsidiary of the Atchison, Topeka and Santa Fe, secured a right-of-way from the Murrieta brothers to construct their line connecting San Diego to Barstow. In 1884, the Temecula Land and Water Company purchased around 14,500 acres from the Murrieta brothers to establish a townsite along the railroad. A depot was completed in 1887, and by 1890 there were 800 living in Murrieta. The town continued to boom, and after the turn of the century saw an increase in tourism when a health spa resort was built at Murrieta Hot Springs, three miles east.

Murrieta's status as a tourist destination lasted until 1935, when the trains stopped running to town. As a result, the town stayed small for a number of decades; by 1980 the population had only reached 2,200. This changed with the completion of Interstate 15, and Murrieta quickly grew as a suburb of commuters working elsewhere in Riverside, Orange, and San Diego Counties. By 1990, the population climbed to over 24,000 and the City of Murrieta was officially incorporated July 1, 1991. Within the next 15 years, the population soared to almost 100,000 and today that number is closer to 115,000 - making Murrieta the fourth largest city in Riverside County.