Arizona is 5-0 for the first time in nearly two decades and is ranked 10th in the Associated Press poll.
USC is 3-2 and coming off a loss to Arizona State that ended with a Hail Mary touchdown pass and dropped the Trojans out of the top 25.
But USC is a 2 1/2-point favorite going into Saturday night's game against the Wildcats at Arizona Stadium, according to Las Vegas oddsmakers.
"That's how misleading records and rankings can be," said Jay Kornegay, vice president of race and sport operations for the Westgate Las Vegas Superbook.
"Rankings, as far as we're concerned, mean absolutely nothing," said Jeff Stoneback, Mirage Hotel and Casino sports book manager.
USC Coach Steve Sarkisian on Tuesday began preparing his players for the trip to Tucson.
The Trojans lost, 39-36, in their last game there in 2012, a defeat that sent then-10th-ranked USC into a downward spiral that ended with an embarrassing Sun Bowl loss to Georgia Tech.
The last seven games between USC and Arizona have been decided by seven points or fewer, including the Trojans' 38-31 victory at the Coliseum last season.
Asked Tuesday if he was surprised the Trojans are favored Saturday, Sarkisian chuckled.
"I don't know — it doesn't matter to me," he said, adding, "Have we been favored in other games? I don't know.
"We're a 3-2 football team, we're going on the road to play the No. 10-ranked team in America. We better get our butts ready to play."
USC has been favored in every game this season except for its Sept. 6 game at Stanford. The Trojans, a three-point underdog, won, 13-10.
Arizona has not played since Thursday, when the Wildcats, a 21 1/2-point underdog, upset previously No. 2-ranked Oregon, 31-24, at Eugene, Ore.
The victory moved the previously unranked Wildcats into the top 10, the largest leap in the AP poll's history since it expanded to 25 teams in 1989.
But Arizona will be the underdog on Saturday.
"We all know why," Arizona Coach Rich Rodriguez told reporters in Arizona on Monday.
USC, which was ranked 16th before its loss to Arizona State, has won 11 national titles and 24 Rose Bowls. Arizona has no national championships and has never played in a Rose Bowl.
Kornegay and Stoneback said in separate telephone interviews that oddsmakers take into account a team's schedule among other factors.
USC, for example, is coming off an emotional loss and could be primed to bounce back as it did against Oregon State after losing at Boston College. Arizona's upset win at Oregon could make the Wildcats susceptible to a letdown experienced by some teams after emotional victories.
USC also is what is known as a "public team," Stoneback said.
And what is a public team?
"A team the public will bet on more," he said, pointing to pro teams such as the Dallas Cowboys and New England Patriots and college teams such as Notre Dame and Alabama.
Kornegay and Stoneback said lines are set to draw equal interest on both sides of the betting board. That the line has barely moved since it was posted proves it is correct, they said.
But Kornegay knows the line will be talked about regardless of the game's outcome.
"If Arizona wins, everyone is going to say, 'Vegas got it wrong,'" he said. "If USC wins they'll say, 'Oh my gosh. What did they know?'"