San Mateo is situated on the San Francisco Peninsula, just 15 miles south from San Francisco. It was named by the De Anza exploration party when they set up camp along the banks of a small creek, now along Arroyo Court, in spring 1776. It is unknown why the Catholic De Anza expedition chose San Mateo, as the recognized Catholic Feast Day for St. Matthew is actually in September. Matthew, one of Christ's apostles, wrote the first book of the New Testament. The name in Spanish translates as Saint Matthew in English.

The small city began to expand after the fire and earthquake in 1906 as refugees moved to the country, although San Mateo also experienced damage. In the post-WWII years, San Mateo became a vibrant town of about 40,000 people. Downtown featured many upscale businesses.

Silicon Valley, which originally evolved in the San Jose area in 1970s as a global center for high technology, has now expanded to include the entire San Francisco Peninsula. In San Mateo itself, many well recognized computer firms have now established headquarters here, ballooning the population to over 100,000.