In the absence of hosts Brazil, Argentina sit top of the CONMEBOL table, while their opponents are in the final automatic position of 4th, and the 28-year-old believes that a win over the Copa America champions will be a crucial step towards qualification.
"Uruguay are a team that in recent years has gained good results and put in good performances and they've been playing together for a long time," he explained to journalists after training on Tuesday.
|WORLD CUP QUALIFYING LATEST
|10/1||Argentina are 10/1 with Bet365 to beat Uruguay 3-0
A win over the Uruguayans would give Alejandro Sabella's team a six-point cushion over Venezuela, who are just outside the qualification places, ahead of Tuesday's match against Chile, but Mascherano is eager to concentrate solely on Friday's match.
"We know we are leaders in the standings, and given that Venezuela don't have a fixture on Friday, the six-point gap would put us well on track for qualification," he added.
"The first thing to think about is Uruguay, knowing three more points to go to Chile with will give us confidence to win again."
The former Liverpool player also spoke about the unfair pressure that coaches such as Sabella are under in Argentina, and suggested they should be afforded more time in which to piece together their projects.
"Maybe the Argentines are accustomed to pressure, especially coaches who are changed on a very fast cycle," he added.
"I think the managers' projects should be given more time, otherwise you're constantly changing and starting from scratch.
"In Europe they are probably given more time. [Sir] Alex Ferguson has been at Manchester United for 25 years but in the first few years he didn't win any titles.
"Arsene Wenger hasn't won anything for seven or eight years but he is still at Arsenal. It happens because it is easier to change one manager than a whole squad."