In 1922, the Mobile County Public School System (MCPSS) began to plan for the construction of a new high school that would serve the entire county, as the facilities of the now venerable 80 years old Barton Academy structure of Greek Revival architecture, in downtown, were becoming overcrowded and suffering from inadequate maintenance and difficult to maintain.

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.

[5] By the fall of 1970, following stringent desegregation efforts in Alabama, 1,500 of the school's 2,140 students were African American.

[3] Murphy students were featured in the Seventeen magazine issue for November 1996 fashion trends in high school.

[citation needed] On December 25, 2012, Murphy High School was hit directly by an EF2 wedge tornado, which caused significant damage to the campus.