The first game between two Los Angeles NFL teams since 1994 highlights week three of the season with a quarterback matchup that could make it worth the lengthy wait.
The Rams offense has impressed in their first two victories under second year quarterback Jared Goff, while Chargers veteran quarterback Philip Rivers should keep it close.
"Yeah, it's a big game," said Chargers coach Anthony Lynn of Sunday's contest at the Memorial Coliseum. "I love playing in the Coliseum as well -- that place, I have a lot of fond memories of that place and it's a great place to play a football game. Should be a lot of fun."
The Rams enter the matchup with a 2-0 record after beating the Arizona Cardinals last week.
Rivers will have to find a way to move the ball against the Rams. Rivers has connected on 73 percent of his passes (57 of 78) for 680 yards and six touchdowns with one interception in the first two games of the season. He ranks third in the NFL in touchdowns.
The Chargers defence will have its hands full with Goff, who has thrown for three touchdowns so far.
Goff is completing 65 percent of his passes for 587 yards and has just one interception.
"To see how Jared has taken off this year and to see him make the transition from me playing against him in college to see how hungry he is to go out there and prove he is one of the top quarterbacks in this league, it helps us," said Rams cornerback Marcus Peters.
Elsewhere, the Philadelphia Eagles will have quarterback Carson Wentz back when they host the Indianapolis Colts, who are playing consecutive road games.
Andy Dalton and the improved Cincinnati Bengals offence will be well-rested when they travel to Carolina to face the Panthers.
The Bengals have their offence revving in high gear, putting up 34 points in back-to-back games to open the season.
Sunday's other games include, Buffalo Bills at Minnesota Vikings, Denver Broncos at Baltimore Ravens, Green Bay Packers at Washington Redskins, New Orleans Saints at Atlanta Falcons, New York Giants at Houston Texans, Oakland Raiders at Miami Dolphins, San Francisco 49ers at Kansas City Chiefs, Tennessee Titans at Jacksonville Jaguars, Chicago Bears at Arizona Cardinals, Dallas Cowboys at Seattle Seahawks and New England Patriots at Detroit Lions.
The Monday night game will feature the Pittsburgh Steelers visiting the Tampa Bay Buccaneers, who have developed into an offensive juggernaut despite the absence of suspended starting quarterback Jameis Winston.