On September 8, 1965, James Madison Junior-Senior High School was formally opened for 2003 students, 793 of whom were Senior High School students. By the end of 1967, Madison Junior-Senior High had reached an enrollment peak of 2700. In January of 1968 the local Junior High School and what was at that time James Madison became James Madison Senior High School. In the fall of 1981, the school population of Madison was extended to include the ninth grade; the enrollment during that year reached a peak of 2236.

In the fall of 1965, the faculty and students of Madison were welcomed to their beautiful new school by the Principal, Mr. Arthur D. Herring, the Assistant Principal, Dr. Dale H. Perkins, and the Dean, Mrs. Rosamund Glosup. These original administrators, teachers, and students—along with members of the community—determined the policies for the new school and decided upon such matters as the selection of the Marlin as the school mascot and the school colors of blue and white with a trace red.

Mrs. Carrie R. McAfee became the Principal in 1974 after Mr. Herring’s retirement from HISD. Her appointment as the first black female principal of a senior high school set an important precedent for the Houston independent School District. Mrs. McAfee remained at Madison until 1989.

Mrs. Ada Cooper was assigned as Principal in 1989. In July 1992, she became HISD’s Director of Grant Writing.

Mr. Warner D. Ervin, former Principal of Ryan Middle School, became the Principal at Madison in July 1992. Madison became a magnet school for Meteorology and Space Science in 1995 with a partnership with Channel 2. In 1997 Madison received a grant from business partner, General Electric for $250,000 for a College Bound Program.

Ms. Gloria J. Legington became the Principal of Madison in July 2000 when Mr. Ervin was promoted to the position of Superintendent of the South District. Ms. Legington had served as the Dean of Instruction at Madison, and prior to that served as the Chairperson for the Career and Technology Department. During her reigning tenure, Madison High School earned the status as a NASA Explorer School.

Dr. Aubrey Todd became the Principal of Madison in August 2008, after the retirement of Gloria Legington. With 16 years of experience as a high school administrator, Dr. Todd’s vision for Madison was to invoke a culture of education as "serious business". After 3 years Dr. Todd relocated to St. Louis, Missouri and became Supintendent.

Mrs. Sonja C. Williams became Principal of Madison High School in July 2010. She had held previous campus leadership roles in Brazos ISD, Angleton ISD, and Alief ISD. During her first year of leadership, Madison was recognized by the Board of Education for having 100 percent of the 2010-2011 senior class apply to a 2-year or 4-year college. Mrs. Williams deemed Madison as "The Heart and Future of the Community" and worked with her faculty/staff and the community to promote college readiness for all students and maintained Madison as an important pillar for the entire community.

Orlando Reyna became the Principal of Madison High School in 2014. Mr. Reyna previously served as Principal of Deady Middle School, where he led turnaround efforts.  

Paolo Castagnoli became Principal of Madison High School in 2017.

Carlotta Outley Brown is a product of HISD schools where she was a proud graduate of James Madison High School in 1979.  Later she matriculated on to college where she graduated from Houston Baptist University earning a dual degree in Elementary Education and History.  Principal Brown is a 31-year educator.  She has been a part of the HISD family since 1991. In July of 2005, Principal Brown was named Principal of Lora B. Peck Elementary. Peck was named a 2008 National Blue-Ribbon School by the U.S. Department of Education.  In addition, she is a Terrel Bell Award Recipient for being 1 of 5 of the best outstanding Principals in the United States for her leadership in turning around a school.  Principal Brown fulfilled her lifelong dream, when she was named the Principal of her Alma Mater, James Madison High School in 2019.

Yolanda Bruce became Principal of Madison High School for the academic calendar year of 2022-2023.

Tanisha Lee became Principal of Madison High School for the academic calendar year of 2023-2024 until December. 

Edgar Contreras became Principal in December 2023 to present.