With Uruguay and South Korea waiting in their subsequent Group H fixtures, Fernando Santos's men are firm favourites to finish as group winners and secure a second straight knockout-stage appearance.
Having failed to qualify four years ago, Ghana booked their ticket to Qatar when they triumphed over West African giants Nigeria in March's playoffs, beating the Super Eagles on away goals following a 1-1 aggregate draw.
Here, Sports Mole looks at how the squads of Portugal and Ghana stack up against each other ahead of Thursday's contest.
PORTUGAL
Most valuable player:
Rafael Leao (£73.5m)
Overall squad value:
£810.2
Most capped player:
Cristiano Ronaldo (191)
Leading goalscorer:
Cristiano Ronaldo (117)
Total caps:
1,068
Total goals:
196
Oldest player:
Pepe (39)
Youngest player:
Antonio Silva (19)
Average age:
26.8
SQUAD IN FULL
Goalkeepers: Diogo Costa (Porto), Jose Sa (Wolverhampton Wanderers FC), Rui Patricio (Roma)
Defenders: Diogo Dalot (Manchester United), Joao Cancelo (Manchester City), Danilo Pereira (Paris Saint-Germain), Pepe (Porto), Ruben Dias (Manchester City), Antonio Silva (Benfica), Nuno Mendes (Paris Saint-Germain), Raphael Guerreiro (Borussia Dortmund)
Midfielders: Joao Palhinha (Fulham), Ruben Neves (Wolverhampton Wanderers), Bernardo Silva (Manchester City), Bruno Fernandes (Manchester United), Joao Mario (Benfica), Matheus Nunes (Wolverhampton Wanderers), Vitinha (Paris Saint-Germain), William Carvalho (Real Betis), Otavio (Porto)
Forwards: Cristiano Ronaldo (Manchester United), Joao Felix (Atletico Madrid), Rafael Leao (AC Milan), Ricardo Horta (Braga), Goncalo Ramos (Benfica), Andre Silva (RB Leipzig)
GHANA
Most valuable player:
Thomas Partey (£32.8m)
Overall squad value:
£187.5
Most capped player:
Andre Ayew (110)
Leading goalscorer:
Andre Ayew (23)
Total caps:
471
Total goals:
68
Oldest player:
Denis Odoi (34)
Youngest player:
Abdul Fatawu Issahaku (18)
Average age:
24.7
SQUAD IN FULL
Goalkeepers: Lawrence Ati-Zigi (St Gallen), Ibrahim Danlad (Asante Kotoko), Abdul Manaf Nurudeen (Eupen)
Defenders: Joseph Aidoo (Celta Vigo), Daniel Amartey (Leicester City), Abdul Rahman Baba (Reading), Alexander Djiku (Racing Strasbourg), Tariq Lamptey (Brighton & Hove Albion), Gideon Mensah (Auxerre), Denis Odoi (Club Bruges), Mohammed Salisu (Southampton), Alidu Seidu (Clermont)
Midfielders: Mohammed Kudus (Ajax), Daniel-Kofi Kyereh (Freiburg), Elisha Owusu (Gent), Thomas Partey (Arsenal), Salis Abdul Samed (Lens)
Forwards: Daniel Afriyie (Hearts of Oak), Andre Ayew (Al Sadd), Jordan Ayew (Crystal Palace), Osman Bukari (Red Star Belgrade), Issahaku Abdul Fatawu (Sporting Lisbon), Antoine Semenyo (Bristol City), Kamal Sowah (Club Bruges), Kamaldeen Sulemana (Rennes), Inaki Williams (Athletic Bilbao)
Read more on Portugal vs Ghana
Click here to read our full preview for Portugal vs Ghana
How Portugal could line up against Ghana
How Ghana could line up against Portugal