The Native American situation changed dramatically after the Spanish began exploring and then colonizing the San Francisco Bay area. Spanish explorer Pedro Fages and his party traveled through Dublin in 1772 as they traveled south from the San Francisco Bay near Martinez through the San Ramon and Amador valleys and into Santa Clara Valley. From then through the early 1800s, Spanish and then Mexican soldiers, missionaries and ranch hands periodically ventured into the valleys. With the establishment and development of Mission San Jose (founded 1797), Native Americans were forced from their villages to live and work at the mission. Many died from illness, overwork, or malnutrition. The mission used the Dublin area to pasture their herds.
In the early 1800s, more Mexican Californians moved into the Dublin, Pleasanton, and Livermore area. Jose Maria Amador started ranching in the area around 1825. He was one of the largest landowners in the Dublin area when he acquired 17,600-acre Rancho San Ramon land grant in 1835.
1846 was a landmark year with the first large movement of United States immigrants coming to the area. Among others, the Murray, Fallon, Harland, and Donner families left the US intending to travel by wagon train and horse to Mexican California. However, when they arrived, the United States had invaded and annexed California during the Mexican American War (1846-1848). Among the immigrants in 1846 were Michael Murray and Jeremiah and Eleanor Fallon. Later they would later settle in the Dublin area and participate in the area’s development.