Saint Francis High School (also spelled St. Francis High School), is an independent, coeducational, college preparatory day school in downtown Louisville, Kentucky, USA. Founded in 1977, it is an outgrowth of St. Francis School, in Goshen, Kentucky, a K-8 school founded on the developmental education model a decade earlier. Both schools are non-sectarian, but maintain an association with the Episcopal Diocese of Louisville, and a historical link to St. Francis in the Fields Episcopal Church in Louisville. The church and the schools are named for Francis of Assisi.

In the mid-1970s, a St. Francis School mathematics teacher, Thomas H. Pike III, and a group of parents decided to found a new high school as a continuation of the lower School. They chose to locate the new school in downtown Louisville, to take advantage of the resources available there and, in part, to set the school apart from the other independent schools in the city. Serendipitously, a Louisville real estate developer, William Receveur, had recently purchased the former headquarters of the Louisville YMCA at 233 W. Broadway and was in the process of renovating the building, erected in 1913, for office and commercial space. The fledgling high school rented the third floor of the old "Y" and opened its doors with a small class of ninth graders, adding grades 10-12 in subsequent years. The school gradually rented out more space in the seven-story building, as other tenants moved out, occupying parts of the ground floor, first floor, second floor and fourth floor by the close of the 2000-2001 school year.
 
As the school approached its 25th year, Pike, who had been serving as head of school since its founding, and the school's directors sought to expand and revitalize St. Francis High School. Following a $6 million fundraising campaign, St. Francis High School and a private partner undertook a major redesign and renovation of the entire building, with the school occupying the northern half and apartments and commercial spaces the southern half.
 
Pike stepped down as head after the 2002-03 school year. Alexandra Schreiber Thurstone '84 is the current head of school.