Holy Cross is a founding member of the Patriot League, with one-quarter of its student body participating in its varsity athletic programs.

Principal facilities include Fitton Field for football (capacity: 23,500) and Hanover Insurance Park at Fitton Field for baseball (3,000), the Hart Center at the Luth Athletic Complex for basketball (3,600) and ice hockey (1,400), the Linda Johnson Smith Soccer Stadium (1,320), and the Smith Wellness Center, located inside the Luth Athletic Complex.

In the last two of these seasons, the team featured pitcher Dick Joyce, who briefly made the major leagues, and third baseman John Peterman, who after a short minor-league career went on to become a successful entrepreneur who was parodied on Seinfeld.

Notable former players include Boston Celtics legends and Naismith Memorial Basketball Hall of Fame inductees Bob Cousy and Tom Heinsohn.

Six-time Patriot League Coach of the Year Bill Gibbons recorded his 500th win early in the 2011–2012 campaign.

Notable former players include Bill Osmanski who went on to win four NFL Championships with the Chicago Bears and two-time Heisman Trophy finalist Gordie Lockbaum.

The Holy Cross golf team has also produced some exceptional golfers including Willie Turnesa who won two US Amateur titles (1938, 1948) and a British Amateur (1947), and Paul Harney who, after earning a medal as the stroke play champion at the 1952 NCAA Golf Championship, won six PGA Tour events and was inducted into the PGA of America Hall of Fame.

[12] Also in 2016, 14 Holy Cross varsity athletic teams received Division I Academic Progress Rate (APR) public recognition awards from the NCAA.

The 14 total teams earning public recognition awards put Holy Cross in the top 10 among all Division I athletic programs.

[15] The name was rediscovered by Stanley Woodward, a sports reporter for the Boston Herald, when he used the term "Crusader" to describe the Holy Cross baseball team in a story written in 1925.

The name appealed to the Holy Cross student body, which held a vote later in that year to decide whether this cognomen or one of the other two currently in use – "Chiefs" and "Sagamores"- would be adopted.

On October 6, 1925, The Tomahawk, an earlier name of the student newspaper, reported that the results of the ballot were: Crusaders 143, Chiefs 17, Sagamores 7.

According to the account, there was a disagreement during the 1870s between Holy Cross students from Massachusetts and Connecticut concerning the schools' baseball uniform colors.

Legend has it that a fellow student with a sense of diplomacy resolved the dispute in the chemistry lab, where he mixed copper sulphate (blue) with iron oxide (red) to produce the color of deep purple.

On November 28, 1942, Holy Cross beat BC in a huge upset by a score of 55–12, a result that proved fortunate for the losing Eagles.

The BC team had booked their victory party for a popular Boston nightclub, but canceled after the upset loss.

In 1986 Holy Cross changed the direction of its football program, joining the Division I-AA Patriot League, and terminated the series.

The last basketball game between the two schools was played on January 17, 2006, a 63–53 win for Boston College at Worcester's DCU Center.