The Arizona Cardinals have been tipped by many to finish with the NFL's worst record, while the Los Angeles Chargers are seen as play-off contenders.
But the Chargers were humbled on their own turf at SoFi Stadium, which will host Super Bowl 61 in February.
The Cardinals are trying to make a fresh start having brought in Mike LaFleur as head coach and released quarterback Kyler Murray, and they dominated possession in a 26-14 win.
Murray, who went on to earn the starting role with the Minnesota Vikings, made a wretched start at home to the Green Bay Packers, coached by LaFleur's older brother Matt.
Murray's first pass with the Vikings was intercepted, and the former first overall draft pick then suffered a concussion before being replaced by veteran Carson Wentz.
Despite falling 22-10 down late in the third quarter, the Vikings fought back to win 39-22, with Justin Jefferson claiming two well-taken touchdowns and a two-point conversion.
The Vikings have had nine starting quarterbacks since Jefferson was named offensive player of the year for 2022, and the wide receiver looked back to his best.