The Rio de la Plata rivals are the Copa América's two most successful nations with 29 titles between them, and they meet in a match that could have huge ramifications on their current campaigns at the Estadio La Portada.
The defending champions look on course to move into the knockout stages after Cristian Rodríguez's winner in an unconvincing display in their opening fixture against Jamaica put them top of Group B at the end of the first round of matches.
Winfried Schäfer's side had more than enough chances to take something from the game but failed to break down a stubborn defence, well marshalled by Godín and José Giménez.
And la Celeste's captain know that they will need a similarly resilient display if they are to stop Argentina - and in particular, Messi - and have a positive campaign.
"In this Copa we want to do good things, so for us to win is good because I told my team-mates that in 10 years with the national team I have never won an opening game. This makes you look at the remaining matches from a different perspective," Godín told La Nacion.
"What happened in the first game is not important. We are going to face the favourites to win the Copa América, with players at a high level that make the difference."We will have to prepare for the game well because it is the only way to counter their individuals. If you do not mark them all it is very difficult to stop Argentina.
"There is no formula to stop Messi, otherwise someone would have already achieved it. There is no single recipe, it's a team effort. We must do it together, because if not it's impossible that he won't hurt us."
Uruguay won the most recent installment of this famous rivalry - a 3-2 success in qualifying for the 2014 World Cup - and may take confidence from seeing Gerardo Martino's side throw away a two-goal lead against Paraguay on their debut.
Argentina had led thanks to goals from Messi and Sergio Agüero and Facundo Roncaglia expects them to be just as lethal despite their disappointment against la Albirroja.
"We have to start thinking a bit more on the pitch and not expect the coach to tell us [what to do] and make the decision ourselves to close ourselves up at the back a bit," he said."If Uruguay tries to match us and we are stopping them well at the back, they will be left unprotected and we know that [Lionel] Messi and [Ángel] Di María and the striker that the coach chooses will always make a difference."
However, Roncaglia may find himself removed from the starting line-up with Pablo Zabaleta available following an ankle injury.
Martino also has Lucas Biglia closer to full fitness and - having come on as a substitute against Paraguay - he could be introduced to stiffen the midfield, with Javier Pastore or Éver Banega forced out.