BYU (2-4, 1-1 Mountain West) is struggling to score points this season and has already fired its defensive coordinator.
Meanwhile, the Horned Frogs (6-0, 2-0) are coming off consecutive shutouts for the first time in 55 years and have the nation's top-ranked defense.
The Cougars are 29-point underdogs, the largest they have been since at least 1985, according to the odds maker RJ Bell of Pregame.com.
Two years ago, BYU was ranked ninth and had won 16 consecutive games before a 32-7 loss in Fort Worth. The Cougars were ranked 16th and at home last year when TCU beat them 38-7 for their only conference loss.