Four-time World Cup winners Italy were stunned in Palermo as Aleksandar Trajkovski - who used to play club football in the Sicilian city - fired past Gianluigi Donnarumma in the second minute of injury time to give North Macedonia an incredible 1-0 victory.
Italy will again be absent from the World Cup in Qatar after also failing to qualify for the 2018 tournament in Russia when they lost in a play-off to Sweden.
That was a traumatic experience for a nation that had previously been to every tournament since 1958, and this failure is all the more remarkable given that they were crowned European champions less than nine months ago.
That success for Roberto Mancini’s side came during a world record 37-game unbeaten run, but four draws in their last five qualifiers last autumn saw them finish second in their group to Switzerland, exposing them to the dangers of the play-offs again.
“It’s hard to explain, it’s such a huge disappointment,” captain Giorgio Chiellini said to RAI.
“We’ve made mistakes since September and we’ve paid for them. We’re distraught.”
North Macedonia, the Balkan nation of just two million people, held Italy to a draw in Turin in 2018 World Cup qualifying and beat Germany away in this campaign before appearing at their debut European Championship last year.
“We won the Italian way against the Italians, a goal from just two shots,” said their coach, Blagoja Milevski.
Penalty miss costs Turkey
They will now go to Porto to face Portugal next Tuesday, after the Euro 2016 winners defeated Turkey 3-1 at the Estadio do Dragao, albeit only after Burak Yilmaz missed a crucial late penalty for the visitors.
The home side were cruising thanks to first-half goals by Brazilian-born midfielder Otavio and Liverpool forward Diogo Jota.
But Turkey’s veteran skipper Yilmaz pulled a goal back in the 65th minute, setting up a tense finish.
Turkey were then awarded a late penalty when a foul on Enes Unal was detected following a VAR review, but Yilmaz put the spot-kick over the bar and Matheus Nunes secured Portugal’s victory in stoppage time.
Turkey have not appeared at the World Cup since coming third in Japan and South Korea in 2002.
Portugal have not missed out on the tournament since 1998 and, at 37, Cristiano Ronaldo’s dream of World Cup glory remains alive.
Meanwhile, Gareth Bale was in inspirational form as his brace secured a 2-1 win for Wales against Austria in Cardiff.
Bale has only played five times for his club Real Madrid this season, and just twice since August, but the Wales captain started at the Cardiff City Stadium and opened the scoring from a stunning 25th minute free-kick.
He then struck again, with a superb hit across goalkeeper Heinz Lindner into the far corner, to double the lead six minutes after half-time.
Wales, bidding to qualify for their first World Cup since 1958, then held on after Austria reduced the deficit in the 64th minute when Marcel Sabitzer’s shot deflected in off Ben Davies.
“I’ll run myself into the ground for this country, we all did tonight,” Bale, who came off right at the end with cramp, told Sky Sports.
Robert Page’s team will be at home in the play-off final but must wait until at least June for that, with the ongoing war in Ukraine meaning their tie away to Scotland remains on hold for now.
Sweden set up a play-off final against Poland after an extra-time strike by Robin Quaison gave them a 1-0 win over the Czech Republic in Solna.
Quarter-finalists in 2018, Sweden got their winner in the 110th minute as Saudi Arabia-based Quaison finished after a one-two with Alexander Isak.
Poland received a bye to the play-off final after would-be opponents Russia were suspended from all international competition until further notice following the invasion of Ukraine.
Scotland and Poland drew 1-1 in a friendly in Glasgow, with Kieran Tierney giving the home side the lead only for Krzysztof Piatek to level with a stoppage-time penalty.