Trey Lance threw his first NFL touchdown and Jimmy Garoppolo excelled but the San Francisco 49ers were forced to hold off a near-miraculous rally from the Detroit Lions in a 41-33 thriller.
Rookie third overall pick Lance was not able to win the starting quarterback job from Garoppolo, yet he still made his regular-season debut at Ford Field on Sunday, and he took his first snap with the Niners on the Detroit 16-yard line on their second drive of the day.
His second snap saw him hit Trent Sherfield for a five-yard touchdown pass and, though Detroit responded with Jared Goff connecting with tight end T.J. Hockenson, Garoppolo's 314-yard performance, which included a 79-yard touchdown throw to Deebo Samuel, scores on the ground from rookie Elijah Mitchell and JaMycal Hasty and a Dre Greenlaw pick-six appeared to have put the game beyond all doubt.
San Francisco led 41-17 with under five minutes remaining in the fourth quarter, but a Jamaal Williams short-yardage plunge followed by a two-point conversion provided Detroit a glimmer of hope that grew brighter when George Kittle was unable to field an onside kick.
The Lions subsequently drove down the field and Goff found Quintez Cephus for a two-yard touchdown and another two-point conversion. They then had a chance to tie the game following a fumble from Samuel, but Detroit could not complete an incredible comeback to force overtime.
Samson Ebukam's pressure forced Goff into an errant throw, allowing the Niners to breathe a huge sigh of relief.
It was, however, a pyrrhic victory for San Francisco, who lost cornerback Jason Verrett to what head coach Kyle Shanahan believes is a torn anterior cruciate ligament.
Though the 49ers took defensive starters out of the game following Verrett's injury with what eventually proved an insurmountable lead, the ease with which the Lions moved the ball late in the game should be of concern to San Francisco, especially with two of their NFC West rivals enjoying excellent days.
The Arizona Cardinals and the Seattle Seahawks each won comfortably. Kyler Murray threw for four touchdowns and ran for another while defensive end Chandler Jones had five sacks in the Cardinals' easy 38-13 win over the Tennessee Titans, while Russell Wilson had four touchdown passes for the Seahawks as they saw off the Indianapolis Colts 28-16.
Steelers stun Bills
While not quite as dramatic as events in Detroit, the Pittsburgh Steelers' win over the Buffalo Bills at Orchard Park was certainly unexpected.
The Bills led 10-0 at the end of the first half, but Josh Allen was sacked three times as the Steelers held a usually explosive offense in check.
And, after a pair of field goals from Chris Boswell, Diontae Johnson's spectacular catch at the back of the endzone in the fourth quarter gave them a lead they would not relinquish.
Ulysees Gilbert III recovered a blocked punt to make it 19-10 Steelers, Mike Tomlin's men going on to close out a 23-16 win that deals an early blow to a Bills team seen as Super Bowl contenders.
Burrow makes winning return
Last year's number one overall pick Joe Burrow made his return from a serious knee injury in the Cincinnati Bengals' clash with the Minnesota Vikings, and it proved a successful one in a thriller at Paul Brown Stadium.
He connected with college team-mate Ja'Marr Chase, the fifth overall pick by the Bengals this year, for a 50-yard touchdown in the first quarter to give Cincinnati a lead that they eventually let slip late in the fourth quarter when Vikings kicker Greg Joseph tied matters at 24-24 with a 53-yard field goal.
That forced overtime, but a Dalvin Cook fumble in Bengals territory handed Burrow and the Bengals the chance to clinch it, and he did just that with a drive that set up Evan McPherson's 33-yard field goal and sealed a 27-24 success.
This year's number one overall pick, Trevor Lawrence, endured a very different day. He threw for 332 yards and three touchdowns with three interceptions as the Jacksonville Jaguars were beaten 37-21 by the Houston Texans.