The powerful Johnson had won his last three events and was the favorite to clinch the famous green jacket, but he hurt his lower back slipping down stairs
in his rental house in Augusta on the eve of the tournament.
The 32-year-old underwent intensive rehab overnight and took to the Augusta practice range Thursday to test his back before pulling out minutes before his 2.03 pm ET starting time.
"Obviously, I want to play more than anything but I just can't swing the club," Johnson told reporters at Augusta.
"I just don't feel like there's any chance of me even competing. It hurts. I was doing everything I could to try to play. I was up pretty much all night trying to get it ready for today."
Instead, it was the 40-year-old Hoffman who made light of the breezy, befuddling conditions to fire a seven-under 65, including four straight birdies on the back nine.
The Las Vegas resident, playing in his fourth Masters, held a four-shot lead over countryman and debutant William McGirt the only other player to break 70.
Hoffman's is the biggest first-round lead at Augusta since Jack Burke's four-shot advantage in 1955.
"The putts started going in the hole - as simple as that sounds," said the world No. 52, who was ninth at the Masters in 2015.
Hoffman's round was all the more remarkable given only 11 players broke par, but the rest of the field will be hoping it was an anomaly -- in the last 11 Masters the winner has been inside the top 10 and within four shots of the lead after round one.
The 37-year-old McGirt, who has missed the cut in three of the four previous majors he has played, said: "It was pretty darn special. Any time to break 70 is awesome.
"I'm lucky enough to know a few members here and I've spoken to a few caddies and they've been happy to share their knowledge with me."
England's two-time runner-up Lee Westwood, 43, finished a stroke further back in third on two under after a run of five consecutive birdies from the 13th.
Veteran Phil Mickelson, who will be 47 in June, ended in a group of eight players on one under as he bids for a fourth green jacket and first since 2010.
Mickelson, who bagged the first eagle of the tournament with a 40ft putt on the second green, is bidding to become the oldest Masters winner ever, eclipsing Jack Nicklaus, who won his sixth Masters title and 18th and final major at 46 in 1986.
Americans Russell Henley, Kevin Chappell and Jason Dufner, England's Matthew Fitzpatrick, Justin Rose and Andy Sullivan, and Spain's Sergio Garcia were the other players at one under.
"Man, every shot was a gut-check moment out there. There was no room for error," Rose, the 2013 US Open champion, told Sky Sports. Ernie Els, who ended level par, said it was so difficult it was "crazy."
World No. 2 Rory McIlroy needs the Masters to become just the sixth player -- after Tiger Woods, Nicklaus, Gary Player, Ben Hogan and Gene Sarazen -- to complete the career grand slam of all four major titles, but he had to dig deep to fight back from three over after 12 to finish level par.
"If someone told me after nine I would shoot even par I would have ripped their hand off for it," McIlroy told Sky Sports. "I'm really pleased with my day's work. I battled out there, I didn't have my best stuff."
American Jordan Spieth, who was bidding for back-to-back titles when he suffered his infamous quadruple-bogey collapse at the 12th last year, banished his demons with a safe par three at the tricky short hole this time around.
But the 23-year-old ran up another quadruple bogey with a nine on the par-five 15th after his third shot with a wedge span back into the water and his fifth flew over the green.
Spieth, who has finished no worse than second on his three appearances at Augusta, hit back with a birdie at the 16th and ended with a three-over 75.
Defending champion Danny Willett of England began with a double-bogey six on the first after driving into trees, and bogeyed the last to finish with a one-over 73.
This year marks the 20th anniversary of Woods' major breakthrough at the 1997 Masters, when he won by a record 12 shots and become the youngest ever winner of a green jacket at 21.
However, the 14-time major champion is missing his third Masters in four years as he continues to struggle with back issues. Woods won his last Masters in 2005 and his last major in 2008.
The day began with an emotional opening ceremony in the absence of four-time winner Arnold Palmer, who died in September aged 86.
Augusta chairman Billy Payne escorted Palmer's widow Kit onto the first tee before placing Palmer's green jacket on a chair.
The legendary golfer's contemporaries and fellow "Big Three" players Nicklaus and Player hit the opening drives to get the 81st Masters under way.