Stanford junior running back Christian McCaffrey won't play in order to begin training for the NFL draft, while North Carolina's Elijah Hood is out because of medical reasons.
The 18th-ranked Cardinal (9-3) will move on with an expanded role for speedy running back Bryce Love while North Carolina might put even more on the plate of junior Mitch Trubisky, arguably the top quarterback prospect for the 2017 draft.
The programs will meet for the first time since 1998 on Friday in the Sun Bowl, which kicks off at 2 p.m. ET in El Paso, Texas.
McCaffrey, the 2015 Heisman Trophy runner-up and two-time All-American, ended his career with 6,987 all-purpose yards. Love, a sophomore, carried 90 times for 644 yards in the regular season, including 111 against Cal.
Love had 160 all-purpose yards and scored the winning touchdown in a 17-10 win at Notre Dame in October, when McCaffrey was out with an injury.
"He's an every-down back," Stanford coach David Shaw said of the 5-foot-10, 187-pound sophomore.
"He's a physical, explosive runner. He's not a small back by any stretch of the imagination. He runs through tackles and he's tough. For a guy who's under six foot, he can push the pile and drive his legs."
While Stanford will be shooting for its sixth consecutive victory, North Carolina stumbled a bit late, losing two of its final three games. The Tar Heels have ACC wins over Pitt, Miami and Florida State to their credit.
Trubisky, in his first season as the starter, has completed 68.9 percent of his passes for a school single-season record of 3,468 yards, with 28 touchdowns and only four interceptions. The Tar Heels have three receivers with 500 yards or more, paced by senior all-conference receiver Ryan Switzer, who has 91 catches for 1,027 yards and five touchdowns.
Hood, who earned third-team All-ACC honors, rushed for 858 yards this season, missing a game-and-a-half due to injury. He has announced he will return next season as a senior. His backup, T.J. Logan, has rushed 101 times for 578 yards and seven scores this year.
Trubisky has not announced if he will enter the 2017 draft.
"Mitch and I have had multiple conversations," said UNC coach Larry Fedora. "He's got a decision to make, and he will make it at some point. My role in that is to give him as much information as possible and to support him and his family in their decision."
This matchup is a contrast in styles, at least offensively. North Carolina runs an up-tempo offense, while Stanford is happy draining the clock behind an old-fashioned, power running attack. The Tar Heels' defense allowed at least 200 yards rushing in eight of their 12 games, and they rank 113th nationally against the run, yielding 235.5 yards per game.
The Cardinal has been at its no-mistake best since inserting quarterback Keller Chryst into the starting lineup after a 4-3 start. He has seven touchdown passes and no interceptions in the past four games. North Carolina is last nationally with one interception.
The Tar Heels are led defensively by defensive tackle Nazair Jones, a redshirt junior who has declared for the 2017 NFL Draft. Jones, who has 62 tackles, including 7.5 for loss, is considered a fifth- or sixth-round prospect by NFLDraftScout.com.
Stanford has a potential first-rounder in junior Solomon Thomas, who was selected the winner of the Morris Trophy as the Pac-12's top defensive lineman, as voted on by the league's offensive linemen. He has 13 tackles for loss, including seven sacks.
The Cardinal was the preseason favorite to win the Pac-12 but fell out of contention in the North division by midseason before bouncing back to get into position for its sixth season with double-digit victories this decade.
North Carolina got as high as 15th in the AP poll before losing at Duke on Nov. 10.
"We've got to finish off our last game," Trubisky said.
"That's been one of our goals, to win our last game and to beat a big name like Stanford, that's going to be a quality win. So we're preparing as hard as we possibly can. We're doing this for each other and for the program as well. This is a big game for us. We need to get this win."