The Manchester City pair helped La Albiceleste to a 2-0 win over Venezuela to reach the last four, where they will face team-mates, Ederson, Fernandinho and Gabriel Jesus.
READ | Aguero assist as Argentina set up Brazil semi-final
READ | Gabriel Jesus the shoot-out hero for Brazil
It is the first time in more than a decade that the two South American giants will meet in the continent’s premier competition and Aguero says the significance is not lost on Lionel Scaloni’s side.
“We will try to do our best, as we have been doing, to work for the shirt,” he told reporters after the game.
“Argentina v Brazil is not played every day, especially in a competition like this. It generates a lot of expectation, not only in our country but in the world.
“We knew that this match was not going to be easy but we are happy to have gone to the semi-finals. Little by little we are getting better.”
The final of the 2007 edition of the tournament is the last time the two nations met in the Copa America, with Brazil easing to a 3-0 victory.
This year, Argentina lost their group stage opener against Colombia, but have improved as the tournament has progressed.
They kept their second clean sheet against Venezuela, with Otamendi producing a solid defensive display and he is hopeful that form can continue into the huge game that follows.
“We knew it would be difficult from the beginning. It took time to take off, we got better,” he said when addressing the media after the last eight victory.
“Now we are in the semi-finals against an opponent where it is a clasico and we hope it will go in favour of Argentina.”
The semi-final takes place on Wednesday 3 July and kicks-off at 1.30am (BST).
