Fernando Santos's men kicked off their World Cup journey with a 3-2 victory over Ghana, while Diego Alonso's men had to settle for a point against South Korea.
The sides now face off for only the fourth time in history across all competitions and the previous three meetings leave little to choose between the teams.
Portugal emerged victorious in the first edition of this fixture back in 1966 thanks to a hat-trick from Jose which secured a 3-0 victory.
Uruguay opened the scoring in the subsequent meeting six years later through Ricardo Pavoni but Jaime Graca struck in the penultimate minute of the first half to level matters.
However, the South Americans were not to be denied at the third time of asking and on the biggest stage too as they claimed a 2-1 victory in the knockout round of the 2018 World Cup.
Edinson Cavani was the matchwinner on the day as he netted twice to render Pepe's goal inconsequential and send La Celeste to the quarter-final of football's biggest tournament.
PORTUGAL VS. URUGUAY HEAD-TO-HEAD RECORD
Portugal wins: 1
Uruguay wins: 1
Draws: 1
Portugal goals:
Cameroon goals:
June 26, 1966: Portugal 3-0 Uruguay (Friendly)
July 02, 1972: Portugal 1-1 Uruguay (Independence)
June 30, 2018: Portugal 1-2 Uruguay (World Cup)
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