Prior to 1917, during the era of segregated school systems in the Southern US, no public high school existed in New Orleans for African-American pupils. Those interested in pursuing an education beyond the eighth grade had to attend one of the city's three private secondary schools for blacks: Leland College, New Orleans University, or Straight College.

In 1917, a group of citizens met to petition the Orleans Parish School System to convert McDonogh 13 Boys' School from a white elementary school to a secondary educational facility for black pupils. The petition was granted and in the fall of 1917, McDonogh 35 became recognized as a four-year high school. McDonogh 35 remained the only public four-year high school for African Americans until L. B. Landry transitioned from an elementary into a high school in 1942. Booker T. Washington also opened its doors in 1942 for African Americans.

Over the years, McDonogh 35 has changed its location four times. The original building at 655 South Rampart Street was destroyed when Hurricane Betsy struck New Orleans in 1965, and for the next four years, the school was temporarily located in the former United States Federal Court House Building at 600 Camp Street. In 1969, students and faculty were moved into the school facility at 133 St.Ann Street that formerly housed McDonogh 41 Elementary School. In September 1972, the facility relocated to 1331 Kerlerec Street in the Tremé neighborhood.

During the 1992-1993 school year, McDonogh 35 was recognized as a National Blue Ribbon School of Excellence by the United States Department of Education.
By April 13, 2006, McDonogh 35 was one of six public high schools that had re-opened since Katrina. Of them, it was the only one in a Downtown neighborhood. According to Philip White, the principal, initially, the administration had plans to accommodate 800 students but found fewer due to the effects of the hurricane. One month later, the enrollment went over 1,000 students and the administration was forced to stop accepting students.

The current facility which opened on August 20, 2015, is located on 16 acres in the Bayou District at 4000 Cadillac Street, the former Phillips/Waters school site. The Louisiana Recovery School District allocated $55 million in Federal Emergency Management Agency recovery funds tied to this site to construct the new state of the art, college preparatory high school.