Mission San Luis Rey de Francia is the 18th in a chain of 21 California Missions established by the Spanish Franciscans. Named after Saint-Louis IX, King of France, the Mission was founded on June 13, 1798 by Father Fermin Francisco de Lasuen in a fertile valley midway between Missions San Diego de Alcalá and San Juan Capistrano. Father Antonio Peyri was assigned the task of administrator and served San Luis Rey for 34 years. Father Peyri supervised the construction of the Mission from the very beginning. Along with his fellow Franciscans, he taught the Native Americans about new methods of agriculture and crafts and introduced them to Christianity.

At an early date, the title "King of the Missions" was given to San Luis Rey. It was the largest of all the missions and once the largest building in California. The Mission complex was built in the shape of a quadrangle and its buildings were constructed of adobe. The quadrangle measured nearly five hundred yards square and covered about six acres of land. At one corner of the quadrangle was the Mission church and cemetery. Adjacent structures housed shops, living quarters and storerooms. Mission farm and pasturelands extended in a radius as far as 15 miles. Mission San Luis Rey raised livestock and produced 67,000 bushels of grain in a single year. More baptisms, marriages and funerals were performed in a shorter period of time than at any other mission.

The Mexican Government administered life as the Mission flourished until 1834 when secularization took place in the Mission. In 1846, Mexican Governor Pio Pico sold the Mission for $2,437.00. The Mission's property was divided up, its buildings stripped of all material goods and the Mission left for ruin. The Mission was abandoned except during the Mexican War and shortly thereafter when the United States troops, including the famous Mormon Battalion, were quartered here. The Mission was incorporated into the United States in 1850 when California became the 34th state of the Union. A patent and proclamation restoring Mission San Luis Rey to the Roman Catholic Bishop of Los Angeles was signed by President Abraham Lincoln on March 18, 1865, less than one month before his assassination. However, the Mission remained abandoned for an additional 30 years.

In 1892, a group of Franciscans from Zacatecas, Mexico arrived at the Mission to take up residence. Father Joseph Jeremiah O'Keefe, an Irish born, Spanish-speaking Franciscan, came shortly thereafter to San Luis Rey to supervise the Mexican Franciscans and began the arduous task of restoring the Mission with hopes of making it a Franciscan Missionary college. After preliminary repairs, Bishop Mora rededicated the church building on May 12, 1893. Father O'Keefe remained at the Mission until 1912, overseeing the first major reconstruction of San Luis Rey. Through the hard work of the Franciscans led by Father O'Keefe (the re-builder), the Mission was brought back to life. The years following Father O'Keefe's departure have seen gradual, yet extensive, restoration. Further improvements and the reconstruction of Mission structures have almost completely restored the Mission to its early grandeur. Mission San Luis Rey was designated a National Historic Landmark in 1970. However, the Mission does not receive any Federal, State or church funds for its support. The Mission depends upon the generosity and support of its volunteers and visitors to continue the restoration efforts so that Mission San Luis Rey will remain the "King of the Missions".