SANTA CLARA, Calif. � The 49ers' season opener headed for a frantic finish Sunday, and we all know how poorly that turned out their last game, in Super Bowl LIV.
This time, too, the 49ers failed to protect a fourth-quarter lead, doomed again by the opposing quarterback's heroics amid busted coverage and failed containment.
And once again, Jimmy Garoppolo could not rally the 49ers on a last-gasp drive.
The 49ers' fate was sealed this time once Garoppolo threw a fourth-down incompletion from the 16-yard line with 33 seconds remaining, and the Arizona Cardinals emerged with a 24-20 upset win at Levi's Stadium, where no fans were allowed in because of COVID-19 precautions.
The Arizona Cardinals' Kyler Murray proved as elusive and maddening as Kansas City Chiefs' Patrick Mahomes did in the Super Bowl, where the 49ers blew a 20-10 lead and fell 31-20. Murray sandwiched a pair of touchdown drives around a Garoppolo touchdown pass to Jerick McKinnon in the fourth-quarter follies.
Arizona went ahead for good on Kenyan Drake's 1-yard touchdown run after DeAndre Hopkins' 33-yard, near-touchdown reception against the 49ers' busted coverage.
Murray proved tough to defend (231 passing yards, 91 rushing yards). He weaved past the 49ers defensive front, up the hashmarks and then beat the 49ers' safeties to the pylon for a 22-yard, go-ahead touchdown with 10:26 remaining.
Here are the highs, lows and all you need to know from the 49ers' opener:
_ GAROPPOLO LINE: Garoppolo started hot but finished 19-of-33 for 259 yards with two touchdowns and no interceptions.
His first quarter was way better than his last in the Super Bowl, as he completed 7-of-9 passes for 135 yards with one touchdown, no interceptions, one sack and a 155.8 rating. Then came an array of off-target passes � one of which led to Kittle's knee injury, one that slipped out from his grasp on a possible double clutch � and a couple sacks. By the way, Garoppolo wore a brace on his left knee, after not doing so the latter part of training camp.
_ FAST START: Speed demon Raheem Mostert scored on a 76-yard touchdown pass to open the 49ers' second possession, a sudden score that put the 49ers ahead 10-0 only 5:07 into their opener. Making his first career start, Mostert came out of the backfield, curled around left tackle Trent Williams, cut inside past rookie linebacker Isaiah Simmons then zipped into open field beyond safety Chris Banjo.
In Mostert's last action on the home field, he ran for a franchise-record 220 yards and four touchdowns in the NFC Championship win over Green Bay.
_ KITTLE INJURY SCARE: Tight end George Kittle was held without a second-half catch, all after sustaining a blow to his left knee and gingerly walked with the 49ers team doctor into the locker room 30 seconds before halftime. Kittle played throughout the second half and finished with four receptions for 44 yards, and a 9-yard run.
On the injury, Kittle's knee was hit by Arizona Cardinals safety Budda Baker as Jimmy Garoppolo's second-down pass from the 8-yard line sailed high over Kittle on the far left side of the formation. Last Halloween, Kittle got knocked out of the 49ers' win at Arizona, and injuries to his ankle and knee kept him out the next two games.
_ COVERING HOPKINS: Richard Sherman, strictly a left cornerback most of his previous nine season, strayed at times to shadow DeAndre Hopkins. Other times, Emmanuel Moseley covered the former Houston Texans star. Hopkins had 14 catches for 15 yards, capped by his 33-yard catch that set up Drake's go-ahead touchdown
_ NOT SO CLUTCH: The 49ers opened 0-for-8 on third-down and also failed on their first fourth-down call, a Raheem Mostert run from the 1 that got stopped short of the goal line. They broke through late in the third quarter with a third-and-8 conversion, Kendrick Bourne making a 16-yard catch. But Garoppolo's ensuing third-down throw sailed incomplete.
_ OFFICIATING DRAMA: Several second-half penalties went against the 49ers defense, almost all coming on questionable calls. Dre Greenlaw and Kerry Hyder got flagged for unnecessary roughness hits on Kyle Murray after he gave himself up on scrambles.
Also K'Waun Williams' holding call nullified a third-down throwaway by Murray in the end zone, and Emmanuel Moseley drew a pass-interference penalty on a deep ball to Christian Kirk.
_ UGLY SEQUENCE: Dontae Johnson was unable to prevent Ezekiel Thompson's rush up the middle to block a 49ers punt on their third possession. One snap later, Chase Edmonds scored on 10-yard reception after beating linebacker Kwon Alexander to the right pylon. That shrunk the 49ers' lead to 10-7 with 6:55 to go in the first quarter.
_ MURRAY'S LAW: Murray, last year's NFL Offensive Rookie of the Year, proved as elusive as expected, even against the 49ers' notorious pass rush. Especially against that pass rush. Rather than sit in the pocket and get sacked, he scrambled, and a 22-yard run in the fourth quarter put the Cardinals ahead 17-13 with 10:26 remaining. The 49ers' first sack of Murray did not come until after halftime, and it came from newcomer Kerry Hyder.
_ WIDE RECEIVER WOES: Add backup Richie James to the wide receivers' injury ward. He was ruled out in the fourth quarter with a hamstring injury. Deebo Samuel (foot) went on injured reserve Saturday and rookie Brandon Aiyuk (hamstring) was inactive.
Perhaps the 49ers sign veteran Mohamed Sanu. Or will it be Kevin White, Jauan Jennings or River Cracraft rescuing them from practice squad.
Starting wide receivers Kendrick Bourne (2 catches, 34 yards) and Dante Pettis (0 receptions, 1 target) were ineffective.
_ GOAL-LINE FAIL: Kyle Shanahan lost a second-quarter challenge whether Raheem Mostert scored on a fourth-and-goal run from the 1. The 49ers reached the 1 on a 16-yard, third-quarter run by Jerick McKinnon. The Cardinals took over 12 { minutes before halftime.
_ SAFETIES TOP PLAYS: Jaquiski Tartt's fourth career interception � and the first by a 49ers starting safety since 2018 � came off a Dre Greenlaw tip 2 { minutes before halftime in Cardinals territory.
Free safety Jimmie Ward made a couple noteworthy plays, too, especially a third-down pass breakup on a blitz in the third quarter.
_ TRENT'S RETURN: Trent Taylor, after sitting out last season with a foot injury, reprised his return-specialist role. As a third-down slot receiver, he deflected a third-down overthrow by Garoppolo to save a potential pick-six into the hands of Patrick Peterson. Taylor made a nice block to help spring Jerick McKinnon for a 9-yard reception to the Cardinals' 14 after the two-minute warning.
_ THE OTHER TRENT: Left tackle Trent Williams' debut featured a devastating, down-field block in the first quarter. It was the first time since 2006 than anyone other than Joe Staley had started at left tackle; Staley retired this offseason.
_ KINLAW DEBUT: Defensive tackle Javon Kinlaw, the 49ers' top draft pick, did not start but did flash on a couple plays. He got in the backfield fast to help stop Kenyan Drake on a 1-yard, second-quarter run. However, Kinlaw easily got pushed back on a third-and-1 conversion run in the third quarter.
_ STARTING JOBS: Answering the mysteries at the few starting spots up for grabs, the 49ers went with cornerback Emmanuel Moseley (over Ahkello Witherspoon), center Hroniss Grasu (over Daniel Brunskill, who started at right guard over Tom Compton).
_ COLEMAN'S CALL: Running back Tevin Coleman suited up despite health concerns amid the wildfire-induced smog. Coleman's sickle-cell trait makes him more vulnerable to hazardous air. His best action came in the fourth quarter with a 6-yard catch and10-yard run that put the 49ers at the Cardinals' 32 with 2 minutes remaining. Coleman was kept him out of two recent practices once the AQI breached 150, including Friday's session with an AQI near 200.
_ AIR CHECK: Unhealthy air did not prompt the NFL to reschedule kickoff as the air-quality index (171) remained below the league's 200 AQI threshold for such a change. The game's official weather: Hazy, 66 degrees, 68-percent humidity, 6 mph winds.
_ 49ERS DEBUTS: Making their 49ers debuts were Jerick McKinnon, Jordan Reed, Trent Williams, Tom Compton, Hroniss Grasu, Kerry Hyder and rookies Javon Kinlaw, Colton McKivitz and Charlie Woerner.
_ SOCIAL-JUSTICE AWARENESS: McKinnon and Richie James appeared to squat by the 49ers' bench rather than stand with teammates during the national anthem, which played out while the Cardinals remained in their locker room. Thirty minutes before kickoff, the 49ers also lined up on their goal line � coach Kyle Shanahan between Garoppolo and Dee Ford _ as "Lift Every Voice and Sing" was played in accompaniment with the NFL's "It Takes All of Us" and "End Racism" messages for the social-equality and pandemic awareness campaigns.
Garoppolo, tight end George Kittle and linebacker Fred Warner were among the 49ers who took the field about two hours before kickoff in a NFLPA-issued T-shirt that read, on the front, "Injustice against one of US is injustice against all of us," and, on the back, "End Racism." Other players and staff wore T-shirts emblazoned: "Black Lives Matter."
_ STARTING LINEUPS: The 49ers' offense opened with quarterback Jimmy Garoppolo, running back Raheem Mostert, fullback Kyle Juszczyk, wide receivers Kendrick Bourne and Dante Pettis, tight ends George Kittle, left tackle Trent Williams, left guard Laken Tomlinson, center Hroniss Grasu, right guard Daniel Brunskill and right tackle Mike McGlinchey.
Defensively, the 49ers started: defensive ends Nick Bosa and Arik Armstead; defensive tackles Solomon Thomas and D.J. Jones; linebackers Fred Warner and Kwon Alexander; cornerbacks Richard Sherman, Emmanuel Moseley and K'Waun Williams; and, safeties Jimmie Ward and Jaquiski Tartt.
_ INACTIVES: Neither wide receiver Brandon Aiyuk (hamstring) nor center Ben Garland (ankle) suited up as potential starters. Other 49ers out: cornerback Jason Verrett (hamstring), quarterback C.J. Beathard, linebacker Demetrius Flannigan-Fowles and Kentavius Street.
The Cardinals did not suit up running back Eno Benjamin, quarterback Brett Hundley, safety Dionte Thompson and offensive linemen Josh Jones and Josh Miles. Wide receiver KeeSean Johnson, an East Palo Alto native, is on the NFL's COVID-19 reserve list.
Aiyuk, a first-round draft pick, will sit out after practicing only twice in limited fashion last week because of an Aug. 23 hamstring strain.
Garland, last season's starting center in the Super Bowl, was also limited in two practices by an ankle sprain dating back to Aug. 18.
