Derrick Barnes punched in three touchdowns in a 2:29 span of the first half and four overall as Holy Cross pounded Holmes, 42-7 on Friday.
Xavier Abernathy and Dylan Couch also ran in TDs for the Indians, who won their second straight season opener over the Bulldogs,
Neither team scored in the first quarter, but the Indians found the end zone four times in the second to blow it open by halftime. Barnes scored with 2:46 left in the half and again 20 seconds later before capping the half with a TD in the closing seconds.
Barnes rushed for 816 yards and 12 scores last year.
In last year's opener, Holy Cross beat Holmes, 24-20. Holmes had notched victories in 2012, 2013 and 2014 vs. Holy Cross.
Holmes will host Paris next Friday week while Holy Cross remains in Covington to face Walton-Verona on Saturday.
