Cristiano Ronaldo was sent off as Republic of Ireland stunned Portugal with a 2-0 win and forced Roberto Martinez's side to wait to qualify for the 2026 World Cup.
The reigning Nations League holders knew a win would be enough to secure their place at next summer's tournament, but a Troy Parrott double put an end to that possibility.
The former Tottenham - and current AZ Alkmaar - striker opened the scoring just after the 15-minute mark with a close-range header, before doubling Ireland's advantage on the stroke of half-time.
Portugal's hopes of earning a comeback were harmed when talisman Ronaldo was sent off for swinging an elbow at defender Dara O'Shea off the ball.
Ronaldo was initially shown a yellow card for the incident, but saw the caution upgraded following a VAR review.
The result means that Portugal will now have to beat Armenia on Sunday to secure their place at the World Cup, while Ireland play Hungary on Sunday, knowing a win would guarantee at least second in the group.
France book World Cup spot as Italy force Norway to wait
Elsewhere, France booked their tickets to North America as a Kylian Mbappe double helped Didier Deschamps' side overcome Ukraine 4-0 at the Parc des Princes.
Mbappe scored either side of Michael Olise's goal before Liverpool's Hugo Ekitike rounded off the scoring to ensure that Les Bleus confirmed their place, having made it to the final in each of the last two World Cup's.
Earlier, Erling Haaland continued his incredible goalscoring form as Norway demolished Estonia 4-1 to all but secure their qualification.
Four goals in 12 second half minutes, two coming from the Manchester City striker, put Stale Solbakken's team in command and leave them on the brink of qualifying.
Norway would have secured their passage had Italy failed to come out on top against Moldova. However, late goals from Gianluca Mancini and Francesco Pio Esposito meant that the Azzurri delayed what appears to be the inevitable.
Norway will travel to Italy for their final qualification game, with the hosts needing to win and produce a 17-goal swing in order to leapfrog the current Group I leaders.
