In the 1920s, Bishop Hugh Charles Boyle of the Diocese of Pittsburgh started a program to expand diocesan involvement in education beyond the existing parish schools founded by the predominantly Catholic immigrant population of the city.

[5] Although the school initially took students only from the central neighborhoods of Pittsburgh, the decline of regional equivalents such as North Catholic and South Catholic, following both schools' gradual switch to coeducation, eventually attracted students from a more comprehensive geographic and socioeconomic range.

[8] The school has an athletic history that includes championships for track and field, soccer, swimming, rowing, bowling and football.

Fencing, table tennis, Ultimate frisbee, and disc golf are offered as club sports.

In 2013, the Central Catholic Rowing Team won its first gold medal at SRAA nationals, defeating their rivals, St. Joseph's Prep.

[15] In 2015, Central Catholic's undefeated club Ultimate Frisbee team won the Division II PHUL championships, defeating their rivals from Bethel Park.

[16] The varsity baseball team also won the 4A WPIAL Championship, defeating Norwin High School.

In 2018, Central Catholic's varsity golf team won their third consecutive WPIAL title with another record-setting round of 372.

The building has undergone renovations to the classrooms, the dining hall, the library, the theater, the writing center, and other areas.

Renovation of the classrooms included adding flat screen televisions, projectors, and other learning technology devices.

Students also have access to a full-time college counselor, family support services, and a psychologist.