But, after a final 10 minutes described as "somewhat crazy" by coach Pep Guardiola, the Bavarian side emerged victorious Saturday in a remarkable turnaround that will dent rival clubs' hopes of ending a run of three successive domestic championships.
"We knew it would be difficult here as Hoffenheim have always created a few problems for us in the last few years," Guardiola told reporters.
But the Spaniard, who had been criticized before the game by former Bayern coach Ottmar Hitzfeld for letting homegrown players leave, could not have expected to be a goal down after just nine seconds.
Kevin Volland equaled the record set on August 23, 2014 by Bayer Leverkusen's Karim Bellarabi when he capitalized on David Alaba's poor backpass to score with his team's first touch of the ball.
"It was a gift. I was in the right place and was able to react to the misplaced pass," said Volland, who is good friends with fellow Germany international Bellarabi.
Bayern equalized just before halftime through Thomas Muller, but the home side seemed poised to regain the lead when his fellow 2014 World Cup winner Jerome Boateng was sent off for two bookings for handball in successive minutes -- the latter as he tried to block a free-kick.
With a sellout 30,000 home crowd watching expectantly and hoping for a first win in 15 matches against Bayern since rising to German football's top tier in 2008, Eugen Polanski struck his penalty kick against the post.
And then, to rub salt in the wound, substitute Robert Lewandowski slid home a last-minute winner from a cross by new signing Douglas Costa, who was also instrumental in Muller's goal -- which the forward put into the net from close range with his thigh.
"The disappointment outweighs everything," Volland said. "We suffered a 2-1 defeat in the 90th minute, despite playing well and having had the chance to finish the job.
"We didn't manage to do it and we were punished. It's a bitter disappointment."
Bayern's second successive victory left the team top of the table on goal difference above Leverkusen, which won 1-0 at Hannover thanks to Hakan Calhanoglu's 18th-minute goal.
They can be joined on six points by Borussia Dortmund or promoted Ingolstadt, who both won in the opening round last weekend and meet on Sunday.
In Saturday's other games, Hamburg bounced back from the 5-0 crushing by Bayern to beat Stuttgart 3-2 thanks to late goals from Pierre-Michel Lasogga and Johan Djourou, having trailed 2-1 at halftime before the visiting side had Florian Klein sent off.
Last season's runner-up Wolfsburg drew 1-1 at Cologne thanks to an 83rd-minute equalizer by Denmark striker Nicklas Bendtner, while Schalke was held to the same scoreline by promoted Darmstadt. Eintracht Frankfurt and Augsburg also drew 1-1.
English Premier League
Manchester United dropped its first points of the English Premier League season after being held 0-0 at home by Newcastle on Saturday.
Manager Louis van Gaal gave former Bayern star Bastian Schweinsteiger his first start in midfield, but United -- after two successive 1-0 victories -- created few chances after captain Wayne Rooney had an early effort ruled out for offside.
The result left United second on goal difference behind Leicester, which considered its excellent form under new manager Claudio Ranieri by coming from behind to draw 1-1 at Tottenham.
Leicester avoided relegation last season after a heroic late run which was not enough to save Nigel Pearson from the sack, but his Italian successor remains unbeaten.
Algeria winger Riyad Mahrez equalized in the 82nd minute with his fourth goal this season immediately after teenage midfielder Dele Alli put the London side ahead.
Crystal Palace moved up to fourth win a 2-1 win at Aston Villa thanks to a late winner from debutant Bakary Sako, while promoted Bournemouth celebrated its first top-flight win as Callum Wilson netted a hat-trick in a 4-3 success at West Ham.
Former Spurs striker Jermain Defoe earned Sunderland its first point this season under Dick Advocaat, canceling out Bafetimbi Gomis' opener for Swansea, while Norwich and Stoke also drew 1-1.
Italian Serie A
Last season's runner-up Roma started the new Italian season Saturday with a 1-1 draw at Hellas Verona.
Italy midfielder Alessandro Florenzi leveled from long range five minutes after Bosko Jankovic put the opener past Roma's new goalkeeper Wojciech Szczesny -- signed on loan from Arsenal -- just past the hour mark.
Roma's city rivals Lazio, third last season, began the 2015-16 Serie A campaign with a 2-1 win at home to Bologna.
Argentine midfielder Lucas Biglia opened the scoring for Lazio before new Dutch signing Ricardo Kishna, 20, netted on his debut for the capital club.
Spanish La Liga
Atletico Madrid kicked off the new Spanish season with a 1-0 victory over promoted Las Palmas.
French forward Antoine Griezmann, Atletico's top scorer as the club finished third in 2014-15, scored the only goal in the 16th minute.
Espanyol beat Getafe 1-0, while Real Sociedad drew 0-0 at Deportivo la Coruna.