The Ohlone Indians inhabited the region of what is now the Mission District for over 2,000 years. Spanish missionaries arrived in the area during the late 18th century. They found the Ohlone living peacefully in a village at the edge of a lagoon, hunting and gathering. It was here that a Spanish priest named Father Palou founded Mission San Francisco de Asis on June 29, 1776. This period marked the beginning of the end of the Ohlone culture.
The Mission was moved from the shore of Laguna Dolores to its current location in 1783. Franciscan friars are reported to have employed Ohlone slave labor to complete the Mission in 1791. Many native Indians were forced to flee the area, and the Indian population at Mission Dolores dropped from 400 to 50 between 1833 and 1841. Mexican and Spanish ranches continued in the area until 1849.
During European settlement of the City in the 19th and 20th century, large numbers of Irish and German immigrant workers moved into the area. Development and settlement intensified after the 1906 earthquake, as many displaced businesses and residents moved into the area, making Mission Street a major commercial thoroughfare. In 1926, the Polish Community of San Francisco converted a church on 22nd Street and Shotwell Street and opened its doors as the Polish Club of San Francisco, referred to today as the "Dom Polski", or Polish Home.
The Irish American community made their mark during this time, with notable people like etymologist Peter Tamony calling the Mission home. During the 1940-1960s, large numbers of Mexicans moved into the area as whites moved out, giving the Mission the Latin character it is known for today. During the 1980s and 1990s, the Mexican population was joined by large numbers of immigrants and refugees fleeing civil wars from Central and South America.
Despite rising rents and housing prices, gentrification, many Mexican and Central American immigrants continue to move into the Mission district.