The Croats, however, hope to avoid relegation into the UEFA Nations League B as they are level with Sweden at the bottom of the Group 3 table going into the final matchday.
Portugal's 10-match unbeaten run in the UEFA Nations League came to an end against France, with N'Golo Kante netting early in the second half to give Les Blues a 1-0 win that ensured they finished top of Group 3.
Croatia, meanwhile, suffered a shock defeat away to Sweden, with the hosts scoring through Dejan Kulusevski and Marcus Danielsson to lead 2-0 going into the break.
Danielsson's own goal in the 82nd minute courtesy of an Ivan Perisic header ensured the game came alive late on, but the Swedes held on for a 2-1 win.
Croatia now need to match or better Sweden's result against France on the final matchday to stave off relegation.
Croatia vs Portugal Head-to-Head
Croatia have never defeated Portugal in the six times they have faced each other, managing only two draws while A Selecao have won four times.
The pair last faced each other in the opening game of Group 3, with Portugal running out comfortable 4-1 winners.
Croatia form guide: W-W-L-D-L
Portugal form guide: D-D-W-W-L
Croatia vs Portugal Team News
Zlatko Dalic already had plenty of headaches ahead of this game, with Andrej Kramaric, Marcelo Brozovic and Domagoj Vida not making the squad due to the coronavirus. Duje Caleta-Car added to those headaches by picking up another yellow card against Sweden, which means he's suspended for this game.
However, Dejan Lovren is back and is expected to partner Wolfsburg centre-back Marin Pongracic in defence. Josip Juranovic came on to replace the injured Filip Uremovic at right-back against the Swedes, and may reprise his role although Tin Jedvaj is also an option.
Injuries: Filip Uremovic
Covid-19: Andrej Kramaric, Marcelo Brozovic and Domagoj Vida
Suspensions: Duje Caleta-Car
In what is effectively a dead rubber for his side, Fernando Santos is likely to change his entire XI against Croatia. The Portuguese manager copped a lot of criticism for not starting in-form Diogo Jota against France, so the Liverpool attacker is sure to start.
Renato Sanches picked up an injury against Andorra so is doubtful for this game, with Ruben Neves likely to replace him alongside Joao Moutinho. The likes of Cristiano Ronaldo, Joao Felix and Bruno Fernandes are sure to be rested.
Doubtful: Renato Sanches
Croatia vs Portugal Predicted Lineups
Croatia Predicted XI (4-2-3-1): Dominik Livakovic (GK); Tin Jedvaj, Marin Pongracic, Dejan Lovren, Borna Barisic; Mateo Kovacic, Luka Modric; Josip Brekalo, Nikola Vlasic, Ivan Perisic; Ante Budimir
Portugal Predicted XI (4-2-1-3): Anthony Lopes (GK); Nelson Semedo, Ruben Semedo, Domingos Duarte, Mario Rui; Ruben Neves, Joao Moutinho; Diogo Jota; Trincao, Paulinho, Pedro Neto
Croatia vs Portugal Prediction
Croatia looked quite uncertain at the back against Sweden, but with relegation on the line, they might be able to dig deep and thwart their Portuguese opponents, who will be playing a second string side.
However, such is Portugal's squad depth that they can still name an impressive lineup, with Diogo Jota sure to cause trouble in what might be a stalemate.
Prediction: Croatia 2-2 Portugal
Where does Mane rank in Paul Merson's 5 greatest Liverpool signings of the Klopp era? Click here