The European champions began their campaign with two consecutive draws before getting back on track with big wins against Serbia and Lithuania in their last two games.
Nevertheless, that sluggish start means they are five points behind Ukraine, who currently top Group B and only a big win will do for Fernando Santos' side against Luxembourg.
Luxembourg are winless in their last six games, but prior to that run the tiny nation had enjoyed a fine record, winning five of their previous eight games.
Portugal vs Luxembourg Team News
Fernando Santos has a wealth of attacking options at his disposal with Cristiano Ronaldo, Joao Felix, Bernardo Silva and Goncalo Guedes all included in the squad.
Lokomotiv Moscow midfielder Joao Mario has been rewarded with a recall, while Olympiakos centre-back Ruben Semedo is involved for the first time.
Portugal vs Luxembourg Preview
Portugal have enough firepower to cause any team in the world problems and the side have netted nine goals in their last two qualifiers.
Cristiano Ronaldo's four goals against Lithuania last month underline that the 35-year-old shows no signs of slowing up when it comes to his phenomenal international strike record and he will surely be licking his lips at the prospect of facing Luxembourg.
Another victory for the Portuguese is surely on the cards and perhaps the best way of getting any value is investing in the hosts to get among the goals.
Tips and predictions
Portugal are available at 2.20 to score over 3.5 goals and this should be of interest for those punters looking for a way to be the winners of Euro 2016.
Over the last couple of years this selection has paid out when Portugal have faced much lower-ranked opposition such as Cyprus, New Zealand and the Faroe Islands and could prove profitable once more.
Odds correct at the time of publish. Please gamble responsibly. Check out the latest football odds at Sportsbet.