One week after piling up 59 points in a dazzling season-opening victory over Carolina, Williams and the Bears were restricted to just a single field goal at a rainswept Soldier Field.
A bitterly disappointing home opener for the Bears was compounded by a worrying-looking injury to their franchise quarterback, who hobbled off in the fourth quarter before being taken back to the locker room on a medical cart.
Williams had been in rampant form in last week's win over the Panthers, throwing two touchdowns and rushing for two more.
But the 24-year-old quarterback was given no respite by the Vikings' steely defense, suffering three sacks and coughing up an interception before exiting midway through the fourth quarter after pulling up in agony as he scrambled in the red zone.
Team officials later said Williams had suffered a hamstring injury without giving further details.
The Vikings meanwhile improved to 2-0 thanks to three field goals from Will Reichard. Chicago's lone score came from a 50-yard Cairo Santos field goal.
In other early NFL action on Sunday, the New England Patriots bounced back from their opening loss with a clinical 20-3 defeat of the Pittsburgh Steelers at Gillette Stadium in Foxborough.
Steelers quarterback Aaron Rodgers was sacked four times by the New England defense while the Patriots scores came from a TreVeyon Henderson rushing touchdown and a 19-yard fumble return touchdown from Elijah Ponder.
In Nashville, the Philadelphia Eagles snatched a dramatic 24-20 win over the Tennessee Titans thanks to a last-gasp Darius Cooper touchdown.
The Titans had edged into a 20-17 lead inside the two-minute warning with a Joey Slye field goal.
But Eagles quarterback Jalen Hurts led a nine-play, 65-yard drive that culminated in a three-yard pass to Cooper for a touchdown with nine seconds left on the clock.
In Baltimore, meanwhile, the New Orleans Saints scored 15 unanswered fourth-quarter points to turn a 17-9 deficit into a 24-17 defeat of the Ravens.
Saints quarterback Tyler Shough hit Chris Olave for a 21-yard touchdown before a successful two-point conversion tied the score at 17-17, before Shough's one-yard rushing touchdown with 1min 28sec remaining gave New Orleans the winning score.
The Carolina Panthers made light work of their NFC South rival Atlanta Falcons, who benched QB Cooper Rush and saw rookie Jack Strand throw a pick-six in a 34-3 rout.
Tight end Darren Waller caught two touchdown passes from Bryce Young, while Panthers LB Devin Lloyd shone with 9 tackles and 2 interceptions, including the pick-six.
In Houston, the Cincinnati Bengals beat the offensively poor Texans in a 20-6 win. Ja'Marr Chase made headlines with just his second catch of the game - a spectacular toe-tap catch in the end zone after losing his balance just seconds earlier.
The star receiver combined for 170 yards with colleague Tee Higgins, while the Texans totalled 374 yards, 107 more than the Bengals, without Nico Collins. The Houston Texans fell to 0-2, while the Bengals took the lead in the AFC North with a 2-0 record.
The Green Bay Packers outlasted the 1-0 New York Jets in Jersey, beating them 20-17 in Geno Smith's first home game in MetLife Stadium in ten years.
The Packers tallied under 200 yards and converted 1 of 9 third downs as they amassed 5 fumbles (1 lost), but scored 10 unanswered points in the final eight minutes of the fourth quarter to force overtime, where EDGE Lukas Van Ness capped off a spectacular late display with a half sack to put the Jets on 3rd-and-long and effectively force the deciding punt before Trey Smack made a 26-yard game-winning field goal.