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Holy Cross School fields teams and competitors in many sports. The school currently offers Baseball, Basketball, Bowling, Cross Country, Football, Golf, Powerlifting, Soccer, Swimming, Tennis, Track & Field and Wrestling. Holy Cross currently competes in class 5A of the Louisiana High School Athletic Association.

Holy Cross Football vs. Jesuit Football is the oldest continuous high school rivalry in Louisiana and one of longest running in the United States. The first game was played in 1922 and the two teams have played every year since, including twice in 1963 (once in regular season and again for the state crown, which Holy Cross won).

Holy Cross is also known for its wrestling program and has won the Louisiana state championship in this sport 27 times. They have also had a total of 230 Individual State Champions and 196 State Runner-Up finishes. Twenty-two of those titles were won during the 23-year period of 1945 to 1968; 1951 was the only year in this period when the state championship was not won by the Tigers. These teams were coached by Brother Melchior Polowy who is largely considered the founder of High School Wrestling in Louisiana. The latest championship was won in 2013.

Holy Cross School does not discriminate on the basis of race, color, national or ethnic origin in the administration of its policies.