Holbrook threw for 287 yards and four touchdowns for New Mexico State (3-8, 1-6 Western Athletic Conference), which scored the first three times it had the ball.
NMSU's losing streak to Division I-A schools began with a 34-25 loss to Utah State on Nov. 20, 2004, in Logan.
USU (1-11, 1-7) ended its season with six consecutive losses and posted just one win in a season for the first time since 1984.
Holbrook's four touchdown passes gives him 31 for the season. That broke the previous mark of 30 set by Cody Ledbetter in 1995.
Holbrook, who didn't play in the second half due to blurred vision, also set the school record for most TDs responsible for in a season. He now has 34, breaking Ledbetter's mark of 32 set in 1995.
Chris Williams, who is second in the nation in receiving yards per game (111.4), caught seven passes for 161 yards and three touchdowns.
With a 17-yard catch in the first quarter, Williams broke the NMSU record for most receptions in a season.
He now has 80 this year, besting the old mark of 78 set by Paul Dombrowski in 2005.
In the first quarter alone, Williams had six receptions for 160 yards and three TDs.
Backup quarterback Leon Jackson III was 12-of-25 for 146 yards and two touchdowns for Utah State. Late in the first quarter, Jackson replaced an ineffective Riley Nelson, who was 3-of-6 for 51 yards and one interception.
The interception was returned 34 yards for a touchdown by Courtney Bryan, giving New Mexico State a 28-0 lead late in the first quarter.
Kevin Robinson caught four passes for 101 yards and one touchdown for USU
NMSU is a home next week for it's last game of the season vs LA,Tech