Fernando Santos suffered his first competitive defeat as Portugal coach, with the European champions beginning their 2018 World Cup qualifying campaign with a 2-0 loss to Group B rivals Switzerland, who ended the match with 10 men.
Since taking over from Paulo Bento in September 2014, Santos had navigated Portugal through 14 non-friendly matches without loss, winning Euro 2016 in the process, but that run came to an end at St Jakob-Park on Tuesday.
After a bright start the European champions fell behind in the 23rd minute when goalkeeper Rui Patricio pushed Ricardo Rodriguez's free-kick straight to Breel Embolo, who responded to being selected in place of the injured Xherdan Shaqiri by heading home his second international goal and first since October 2015.
It quickly got worse for Portugal as Admir Mehmedi finished off a rapid break by majestically picking out the top-right corner, sending Vladimir Petkovic's team into half-time with a two-goal advantage.
Having made the most of the few attempts that came their way, Switzerland played in a more defensive manner after the restart and stifled Portugal, who hit the post through captain Nani, wearing the armband due to Cristiano Ronaldo's knee injury, eight minutes from time.
Granit Xhaka was dismissed following two yellow cards in quick succession in second-half stoppage time, but Switzerland had done enough to secure three points against their main rivals for top spot in Group B.
Bernardo Silva was rewarded with a starting berth by Santos after coming off the bench to score and supply two assists in the 5-0 friendly victory over Gibraltar, and he produced a fifth-minute effort that bounced comfortably into Switzerland keeper Yann Sommer's hands.
Portugal continued to apply the early pressure but found themselves behind midway through the half.
Patricio stepped the wrong way when anticipating where Rodriguez would place his 25-yard free-kick, and, despite adjusting to make the save, he was beaten by Embolo's follow-up header.
Switzerland made it two following a swift counter-attacking move seven minutes later.
Blerim Dzemaili led the charge before Mehmedi released Haris Seferovic on the right-hand side of the box and the striker's return pass found the Bayer Leverkusen forward with space to take a touch and curl an exquisite finish into the top corner, with Patricio rooted to the spot.
Raphael Guerreiro responded positively to the setback but was unsuccessful with a pair of attempts before half-time, while Mehmedi was booked for simulation after going down on the edge of the box despite appearing to be caught on the foot by Pepe.
Santos replaced the disappointing Eder and William Carvalho with Andre Silva and Joao Mario for the second half in attempt to spark life into his side, but Switzerland maintained their discipline and proved difficult to break down.
Portugal's final substitution saw Ricardo Quaresma replace Joao Moutinho in the 68th minute, but the result would have been beyond doubt had Dzemaili not skewed narrowly wide from 10 yards three minutes later.
Nani hit the upright with a back-post header off a Quaresma cross in the 82nd minute but Portugal were unable to get on the scoresheet, with the only blemish on the result for Switzerland being the senseless red card for Xhaka before the final whistle.