The Euro 2016 winners were favourites to top Group H when the draw was made.
But they made hard work of their group opener avoiding a late scare.
Uruguay, meanwhile, played out a draw but showed very little goal threat.
A win for Portugal would book their place in the last-16 and top spot could be confirmed if Ghana hold South Korea.
SunSport takes a look at what to expect from Portugal vs Uruguay including our score prediction.
How are they getting on?
Portugal: Expected to reach the knockout stages of the tournament but weren’t as fluid as they’d have hoped against Ghana – despite winning 3-2.
They’ll need unemployed Ronaldo – recently axed by Manchester United – to turn up at clutch moments and lead Portugal to another group victory.
Read the full Portugal vs Ghana match report…
Uruguay: A poor start to their group, being held by South Korea.
Their frontline looked leggy with Luis Suarez up top but record Liverpool signing Darwin Nunez was a bright spark.
Read the full Uruguay vs South Korea match report…
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Any injuries to worry about?
Portugal: Danilo Pereira will be missing for the rest of the group stage after suffering broken ribs in training.
That could see veteran Pepe called upon by boss Fernando Santos.
Uruguay: Barcelona defender Ronald Araujo is expected to miss out having still not fully recovered from thigh surgery at the end of September.
Luis Suarez will likely lead the line again.
Who will be the star men?
Portugal: Ronaldo is the obvious star man with the 37-year-old itching to lift the World Cup.
If given the chance, Rafael Leao – who scored from the bench against Ghana – will shine on the left-hand side.
Joao Felix also has some magic in him.
Uruguay: Suarez and Nunez are the obvious threats, with the latter more likely to unsettle Portugal’s backline.
In the midfield, Real Madrid ace Federico Valverde is a powerhouse.
What’s the head-to-head?
The two sides have met just three times in their history.
Both have one win each with a third game ending in a draw.
The most recent meeting at the World Cup 2018 ended in a 2-1 Uruguay win.
Portugal 2 Uruguay 1