While the hosts kicked off the road to Qatar in perfect fashion last time out, Portugal dropped two points in a highly controversial 2-2 draw with Serbia on Saturday night.
One of the most humiliating nights in Irish football history culminated in Luxembourg forward Gerson Rodrigues lashing home an unstoppable strike in the 85th minute at the Aviva Stadium, as Stephen Kenny's agonising wait for a win went on and scenes of unbridled delirium followed for Luxembourg.
Luc Holtz's side had suffered a 1-0 friendly defeat to Qatar just three days earlier, so they were hardly expected to challenge for a point let alone all three in Dublin, but the Red Lions demonstrated a true display of character to take the spoils and win just their seventh match in World Cup Qualifying since 1934.
However, Luxembourg are certainly not expected to maintain a top-two charge over the coming months, and one victory is their best ever tally in a qualification campaign - which they also achieved during their unsuccessful attempts to make the last three tournaments - so a second triumph in the group would constitute a respectable finish this time around.
Holtz's side moved up to third in the group with their perfect start to proceedings - one point behind Serbia and Portugal with a game in hand - but they have lost five out of their last seven on home soil and their midweek visitors will be fired up after a wretched evening against Serbia last time out.
There was no air of controversy surrounding Diogo Jota's two well-taken headers or the replies from Aleksandar Mitrovic and Filip Kostic, but a dramatic conclusion to Portugal's battle with Serbia eventually led to Cristiano Ronaldo ripping off the captain's armband and storming down the tunnel as the final whistle blew on Saturday.
The five-time Ballon d'Or winner thought he had won it for his side in the dying embers of the match, but Stefan Mitrovic somehow managed to clear his effort off the line before stopping Bernardo Silva's follow-up, although Ronaldo was incensed at the linesman as he felt that the ball had indeed crossed the line.
However, with no goal-line technology available to confirm or overturn the decision, Serbia clung on for a well-deserved point as Ronaldo was booked for his troubles, with Fernando Santos's men enduring an underwhelming start to qualifying after just scraping past Azerbaijan on matchday one.
The reigning European and Nations League champions remain behind Serbia on goals scored following that pulsating draw, but a trip to Luxembourg represents the perfect opportunity for Portugal to stamp their authority on the group before their world-renowned stars return to their respective clubs, and they have lost just one of their last 11 outings away from home.
Furthermore, Portugal have come up trumps in their last 10 meetings with Luxembourg - scoring 34 goals and conceding just one in that time - and the hosts' only win in this fixture came during qualification for the 1962 World Cup as they triumphed 4-2 in October 1961.
Luxembourg have no need to fix what is not broken, and it would be harsh for Holtz to drop any member of the team who started and starred at the Aviva Stadium at the weekend.
Experienced defender Lars Gerson may therefore be restricted to an appearance from the bench, unless the hosting manager opts for a five-at-the-back in order to quell the rampant attack of Portugal.
Brothers Vincent Thill and Olivier Thill look set to man the engine room once more, but the oldest in the family - Sebastien Thill - was an unused substitute against Ireland and is unlikely to force his way into the lineup here.
In a blow to Portugal but a boost to Manchester United, Bruno Fernandes picked up his second booking of the tournament against Serbia and is suspended for the trip to Luxembourg, so Ruben Neves should fill in.
However, Neves's Wolverhampton Wanderers teammate Joao Moutinho was not involved whatsoever last time out and may be forced to miss this one as well, which could give Renato Sanches the opportunity to impress the manager.
Luxembourg possible starting lineup:
Moris; Martins, Mahmutovic, Chanot, Jans; Martins Pereira; Rodrigues, Barreiro, O. Thill, V. Thill; Sinani
Portugal possible starting lineup:
Lopes; Cedric, Duarte, Dias, Mendes; Pereira, Sanches, Neves; Jota, Ronaldo, Felix
We say: Luxembourg 0-3 Portugal
Portugal have flattered to deceive somewhat during their opening two matches, but Ronaldo and co will be more determined than ever to respond to their latest setback this week. The hosts command plenty of respect after overcoming the Irish on their own turf, but Santos's side should have too much quality for the Red Lions, and we can only envisage a comfortable win for Portugal here.
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