St. Anthony's High School is a Roman Catholic college preparatory (grades 9–12) school located in South Huntington, New York on Long Island. The school was founded in 1933 by the Franciscan Brothers of Brooklyn.

Having come to Brooklyn from Ireland at the invitation of Bishop Loughlin, the Franciscan brothers served the Brooklyn diocese as educators and child care providers. The order expanded to rural Smithtown in 1929 with the establishment of Mount St. Francis Novitiate and Normal School, having acquired Mill House, an already old property dating back to the first half of the 19th century, in 1928.

Plans were made for a new Juniorate to board young men at a new location from the Order's existing Juniorate at St. Francis Preparatory School, then in Brooklyn. On August 31, 1933, ground broke on the new facility in Smithtown, New York. The ground-breaking marks the founding of St. Anthony's and its date appears on the school's crest.

Until 1936 freshman began their studies at St. Francis Preparatory School and only sophomores, juniors and seniors boarded and studied at the Smithtown campus.The attendance was modest and never expanded to more than 50 or 60 pupils during the early years. The first five students graduated in June 1935.

In 1949, the Franciscan Novitiate moved from Mill House in Smithtown to Wyandanch, New York and Mill House began to house the Juniorate and faculty. In 1957, the decision was made to expand the school's enrollment as a day school to accommodate a growing Catholic population on Long Island and in the next year, enrollment increased from 40 to approximately 125. The school continued to grow, both in enrollment and with additional facilities on the Smithtown campus until 1984.

On December 5, 1983, Most Reverend John R. McGann announced that, as part of extensive changes in the educational plans of the Roman Catholic Diocese of Rockville Centre, Holy Family Diocesan High School, South Huntington, New York, would close in June 1984, and St. Anthony's High School will re-locate in the Holy Family facility. The two schools, once athletic rivals, were merged and the enrollment and faculty were significantly expanded as a private coeducational high school.

St. Anthony's High School currently is located at the former Holy Family location, at 275 Wolf Hill Road in South Huntington.

The basic curriculum at St. Anthony's includes required courses in Theology, English, Social Studies and Physical Education (4 years); Mathematics, Science, Foreign Language (3 years); Fine Arts (Health, Art, Music or Drama) (1 year). Honors and Advanced Placement courses are offered to students who qualify, with electives in all disciplines. The passing grade at St. Anthony's is 75% to ensure that each student leaves with a higher standard of excellence before entering college and a minimum grade of 80% is required for any letter of recommendation to college.

• Chris Armas ('90), Former USA Soccer National team member, assistant and head coach for New York Red Bulls, head coach for Toronto FC, and coaching staff at Manchester United and Leeds United, head coach of Colorado Rapids.
• Kenny Atkinson, Professional basketball coach for the Cleveland Cavaliers, and formerly for the Brooklyn Nets in the National Basketball Association.
• Dan Barry ('76), Author of Pull Me Up: a Memoir, Bottom of the 33rd: Hope, Redemption, and Baseball's Longest Game, The Boys in the Bunkhouse: Servitude and Salvation in the Heartland, This Land - America, Lost and Found, and City Lights: Stories about New York; New York Times reporter and author of the "This Land" column
• Andre Cisco, American football safety for the Jacksonville Jaguars in the National Football League.
• Philip Daileader ('86), historian and Professor of History at College of William & Mary; in 2012 The Princeton Review named him one of the 300 best professors in America. Video lecturer for The Teaching Company and the History Channel on the Middle Ages and the Crusades.
• John Gregorek ('78), Olympic (1980) middle distance runner for the 3000-m steeplechase.
• Alan Hahn ('89), Sports talk radio host on ESPN Radio and Emmy-award winning Studio analyst on MSG Network.
• Chris Koepplin ('02), former placekicker for the Buffalo Bills and the New England Patriots.
• Nick LaLota ('96), Member of the United States House of Representatives from New York's 1st congressional district since 2023.
• Brian McNamara ('78), actor and Golden Globe nominee.
• Jim Pavese, Former NHL hockey player for the St. Louis Blues, New York Rangers, Detroit Red Wings, and Hartford Whalers.
• Paul Scheer ('94), actor, producer, podcaster and comedian.
• Tom Schreiber ('10), Professional lacrosse player, four-time All-American, all time leading scorer at Princeton.
• Rob Scuderi ('97), NHL hockey player; defenseman and Stanley Cup Champion with the Pittsburgh Penguins (2009) and the Los Angeles Kings (2012).
• Richard Wiese ('77), explorer, Emmy-winning host and producer, President (2002-2006) of The Explorers Club.

• St. Anthony's High School official website
• St. Anthony's Fathers' Guild
• St. Anthony's Mothers' Guild
• St. Anthony's High School Alumni Association website