Top-ranked Notre Dame comes into Saturday's game in Los Angeles leading the series 43-35-5, but the Irish have only beaten Southern California once since 2001.
Here are some of the memorable games:
First Game: Notre Dame backup quarterback Art Parisien threw a 23-yard touchdown pass to John Niemiec with 2 minutes to go to give the Irish a 13-12 victory in the inaugural game. The game was the first regular-season West Coast trip for the Irish two seasons after playing in the Rose Bowl.
Big Crowd: An estimated 120,000 fans, including 99,573 paying customers, crowded into Soldier Field in Chicago to see the Trojans face the Irish. Ray Dahman caught a touchdown pass and kicked the extra point and the Irish won 7-6 after a controversial call when an official ruled an apparent safety for USC was an incomplete pass.
Fourth Quarter Rally: USC scores all its points in the final quarter, capped by a 33-yard field goal by Johnny Baker with 1 minute left, as the Trojans won 16-14 for their first victory in South Bend. The loss ended a 27-game winning streak by the Irish and was the first loss at Notre Dame Stadium, which opened a season earlier, and just the second home loss for the Irish since 1905. USC won its second national championship.
Failed Fake: The game was a scoreless tie late in the first half when top-ranked Notre Dame (8-0) attempted a fake punt on fourth and 22 in its own territory and failed. That set up a 36-yard touchdown pass from Ollie Day to Al Krueger with 5 seconds left in the half, giving the eighth-ranked Trojans a 6-0 lead en route to a 13-0 win before 97,146 fans. The Trojans were the only team to score more than a touchdown against the Irish all season.
Battle of Unbeatens: Top-ranked Notre Dame (8-0) faced No. 3 USC (7-0-1). Emil Sitko broke the game open with a 76-yard touchdown run and Bob Livingstone added a 92-yard score as the Irish clinched the national championship with a 38-7 victory.
The Tie: Bill Martin scored on a 4-yard run with 2:30 left to give USC a 14-7 lead against the second-ranked Irish, who had won 21 straight but had turned the ball over seven times against the Trojans. Notre Dame's Bill Gay returned the kickoff 87 yards to the USC 12 to set up a 1-yard run by Emil Sitko that tied the game at 14 with 35 seconds left. At the time, there was no two-point conversion.
The Upset: The top-ranked Irish (9-0) were upset by Southern California (6-3) when Craig Fertig completed a 15-yard TD pass to Rod Sherman with 1:33 left as the Trojans rallied from a 17-0 halftime deficit to win 20-17. The Irish finished the season ranked No. 3 in posting their first winning season since 1958.
Parseghian's Payback: Two years after being upset by USC, Notre Dame returned to Los Angeles ranked No. 1 with an 8-0-1 record a week after its famous 10-10 tie with Michigan State. The Irish beat the Trojans 51-0 and won the national championship.
Six Touchdowns: Anthony Davis scored six touchdowns, two of them on kickoff returns, and broke five school records as the Trojans beat Notre Dame 45-23.
Streak Ends: Eric Penick scored on an 85-yard run, Bob Thomas kicked three field goals and the Irish defense held Anthony Davis to 55 yards rushing to win 23-14 and end USC's winning streak at 23 games. The Irish went on to win the national championship.
The Comeback: Notre Dame opened a 24-0 lead and held a 24-6 lead at halftime. But Anthony Davis scored on the second-half kickoff to ignite a 35-point third quarter and USC won 55-24, scoring all its points in 17 minutes. USC finished the year ranked No. 2 by The Associated Press, but the coaches awarded them the national championship.
Green Jersey Game: The 11th-ranked Irish, led by quarterback Joe Montana, warmed up in their regular blue jerseys, but came out for the game wearing green jerseys for the first time since 1963 and the Irish cruised to a 49-19 victory over the fifth-ranked Trojans. Irish basketball coach Digger Phelps suggested wearing the green to coach Dan Devine to inspire the Irish. Notre Dame won the national championship.
Commercial Break: Notre Dame quarterback Steve Beuerlein threw four touchdown passes and a pair of two-point conversions for the Irish, who rallied from a 17-point deficit early in the fourth quarter to win 38-37. The Irish won on a 19-yard field goal by John Carney as time expired. The national-television audience missed seeing the game-winning kick live because CBS went to a commercial.
No. 1 vs. No. 2: The only time in the series the two teams met ranked No. 1 vs. No. 2. Tony Rice scored on a 65-yard TD run, tailback Mark Green scored twice on short runs and USC turned the ball over four times as top-ranked Notre Dame beat second-ranked USC 27-10. The Irish were without leading rusher Tony Brooks and top receiver Ricky Watters, who were suspended and sent home after being 40 minutes late for Friday night's team meal. The Irish won the national championship.
Overtime: USC's Brad Otton threw a 5-yard touchdown pass to Rodney Sermons in overtime to give USC a 27-20 victory, allowing the Trojans to avoid their third losing season in 35 years. The loss cost Notre Dame a berth in a major bowl and ended Lou Holtz's tenure as Notre Dame coach with a 100-30-2 record.
Bush Push: Notre Dame came up just short of stopping USC's winning streak at 28 games. Reggie Bush pushed Matt Leinart to help him score the winning touchdown with 3 seconds left, giving the Trojans a 34-31 victory.