[4] The district established a high school in 1906, with 40 students, with a curriculum that covered "English, Latin, Greek, German, history, mathematics, physics, chemistry, bookkeeping, shorthand, typewriting."

The Clifton High School Mustangs[2] compete in over 50 sport programs as part of the Big North Conference, which is comprised of public and private high schools in Bergen and Passaic counties, and was established following a reorganization of sports leagues in Northern New Jersey by the New Jersey State Interscholastic Athletic Association (NJSIAA).

[15] The football team competes in the Liberty Blue division of the North Jersey Super Football Conference, which includes 112 schools competing in 20 divisions, making it the nation's biggest football-only high school sports league.

[18] Interscholastic athletics offered at the school include:[2] The boys' baseball team won the North I Group IV state sectional championships in 1960 and 1961.

[21] The 1967 team won the Group IV state title, defeating East Brunswick by a score of 4–1 in the championship game played at Fairleigh Dickinson University's campus in Madison.

[22] The 2007 boys' soccer team, under the direction of Coach Joe Vespignani, won the North I, Group IV state sectional championship with a 1–0 win over defending Group IV state champion West Orange High School in the tournament final.

The spectacular goal was scored by Manuel Caicedo with a brilliant Bicycle Kick from the penalty spot.

The team moved on to share the Group IV state championship with a 1–1 tie against Manalapan High School.

[28] The 2009 boys' soccer team completed a threepeat as the North I, Group IV state sectional champion with a 3–0 win over Livingston High School.

[31] The 2019 finished the season with a 20–0–1 record after defeating Hunterdon Central on penalty kicks in the Group IV final after a scoreless tie in regulation and overtime.

[37] In 1997, the team finished with a 31–0 record after winning the Group IV title by defeating Middletown South by a score of 3–2 in the finals.

[39][40] The 2007 team won the North I, Group IV sectional championship with a 10–0 win over top-seeded Bloomfield High School.

[49] The girls' soccer team at Clifton, under Coach Dan Chilowicz, shared the Passaic County Championship title with Wayne Valley High School in 2007 with a deadlocked score of 0–0.

The girls' team, led by Stan Lembryk, was declared county co-champion again in 2009 after a 1–1 tie with Wayne Hills High School.

[50] The boys cross country team won the Group IV, public state sectional in the 2021-2022 season.

[53] The group forms the letters "C-H-S", similar to the script "O-H-I-O" of The Ohio State University Marching Band.