The school that would become Howard W. Blake High School of today, began as a vocational school for the community African-American youth. In 1945, the Hillsborough County School Board used an existing warehouse which was already providing vocational training and added more programs. It was called the Don Thompson Vocational High School. Don Thompson was the director of the Vocational Education department for the district. Students from Brooker T. Washington and George Washinton Carver, two all black junior high schools, attended the new school.

In September 1956, Howard W. Blake Comprehensive High School was opened to African American students offering a general education program as well as vocational training. HW Blake Comprehensive High School was named for Howard Wesley Blake, a native of Tampa, who attended Florida A&M University, Claflin University, and Atlanta University. His entire life was geared toward guiding young people to their optimal education and vocational potential.

The students from Don Thompson Vocational High School & George Washington Carver Junior High School attended the new HW Blake Comprehensive High School on the Hillsborough River just west of the North Boulevard bridge. The original HW Blake High School was closed after the 1970-1971 school year due to desegregation and reopened as Blake 7th Grade Center.

The school re-opened in 1997 with a new facility just to the east of the original HW Blake Comprehensive High School on the Hillsborough River. "Comprehenisve" was dropped from the name and became Howard W. Blake High School. It retained the traditional high school curriculum and added a Performing and Visual Arts Magnet component, providing a rigorous college preparatory education and a highly intense performing and visual arts magnet program in which any student within the district may audition to attend. The magnet component includes Music, Vocal and Instrumental, Musical and Dramatic Theatre, Dance, Visual Arts, Television Production, and Creative Writing.