Murphy High School was built in 1926 on 28 acres from the Carlen Estates, to relieve overcrowding at Barton Academy when World War I soldiers returned to complete their education.
Mobile architect George B. Rogers designed seven Spanish Revival Style buildings to serve all of Mobile County's grades 8-11 (12th grade was not included in the academic program in Mobile County until mid-1950s). Construction costs totaled $850,000 for the first six buildings with an additional $200,000 spent on the gymnasium and the indoor pool installed in 1930.
First named Mobile High, the school's name was changed in 1928 to honor Samuel Silenus Murphy, a superintendent of public education for twenty-five years. It is Alabama’s largest public school.
While still called Mobile High School, the yearbook had been called the "Mobile High Annual", which was shortened to"Mohian."
The school was desegregated in 1963 when three African American students gained court ordered admission.