The 2010 Holy Cross Crusaders football team was an American football team that represented the College of the Holy Cross during the 2010 NCAA Division I FCS football season. Holy Cross tied for second in the Patriot League.

In their seventh year under head coach Tom Gilmore, the Crusaders compiled a 6–5 record. Anthony DiMichele, Sean Lamkin and Freddie Santana were the team captains.^[1]

Despite their winning record, the Crusaders were outscored 254 to 249. Their 3–2 conference record tied with Colgate for second-best in the Patriot League standings. Holy Cross' homecoming win over Fordham did not count in its league record, as Fordham had been disqualified from the championship after admitting scholarship players.^[2]

Holy Cross was ranked No. 25 in the preseason national top 25, but dropped out of the rankings after their opening week, and remained unranked for the rest of the year.

Holy Cross played its home games at Fitton Field on the college campus in Worcester, Massachusetts.

Date	Opponent	Site	Result	Attendance	Source
September 4	Howard*	Fitton Field Worcester, MA	W 38–7	6,982	[3]
September 11	at UMass*	McGuirk Stadium Hadley, MA	L 7–31	16,352	[4]
September 18	at Harvard*	Harvard Stadium Boston, MA	L 6–34	21,704	[5]
September 25	at Georgetown	Multi-Sport Field Washington, DC	L 7–17	3,211	[6]
October 2	Fordham	Fitton Field Worcester, MA (rivalry)	W 36–31	10,891	[7]
October 9	Brown*	Fitton Field Worcester, MA	W 17–13	4,973	[1]
October 16	at Dartmouth*	Memorial Field Hanover, NH	L 19–27	3,318	[8]
October 23	at Colgate	Andy Kerr Stadium Hamilton, NY	W 31–24	6,213	[9]
November 6	Lehigh	Fitton Field Worcester, MA	L 17 34	5,892	[10]
November 15	at Lafayette	Fisher Stadium Easton, PA	W 37–27	4,846	[11]
November 20	Bucknell	Fitton Field Worcester, MA	W 34–9	4,297	[12]
*Non-conference game Homecoming ^ Family Weekend