The two favourites to qualify from Group H meet on Monday evening as Portugal face Uruguay at the Lusail stadium.
The 2016 European champions picked up a hard-fought 3-2 win against Ghana in their opening match, while Uruguay were held to a goalless draw by South Korea.
Portugal vs Uruguay latest odds
The two sides' only previous meeting at a World Cup was in the last 16 in Russia four years ago, where two goals from Edinson Cavani helped La Celeste to a 2-1 triumph.
Nevertheless, Portugal are clear favourites offered at 19/20 (1.95) with bet365 to pick up three more points while Uruguay are outsiders at 16/5 (4.20).
The draw is on offer at 5/2 (3.50).
Portugal vs Uruguay first goal scorer odds
Cristiano Ronaldo is the favourite to open the scoring with the former Manchester United striker available at 4/1 (5.00).
The 37-year-old broke the deadlock from the penalty spot in the opening game against Ghana and is ahead of fellow veteran Luis Suarez who is available at 15/2 (8.50).
The former Liverpool forward looked off the pace against South Korea and could be dropped in favour of Edinson Cavani who is available at 9/1 (10.00) the same price at Darwin Nunez.
Portugal vs Uruguay preview
Uruguay were disappointing in their opening match although they improved in the second half, with Real Madrid star Fede Valvderde showing just what an exceptional player he has become.
Portugal are likely to play with more tempo than their South American opponents and we should expect Fernando Santos' men to dominate possession.
Perhaps though there could be some interest in backing the Portuguese to concede in the second half and the majority of matches at this World Cup have see more goals in the second 45 minutes.
Five of Portugal's last seven competitive goals they have conceded have come after the break, while Uruguay scored second half goals in three of the four World Cup qualifiers for which manager Diego Alonso was in charge.
Portugal vs Uruguay tips and predictions
Uruguay are priced at 6/5 (2.20) to score after the break, which looks like a good bet considering their firepower and also how many goals are being scored in the tournament in the second halves of matches.
Odds correct at the time of writing. Please gamble responsibly.