Ronaldo announced he had parted ways with the Old Trafford club by mutual consent on Tuesday following scathing public comments he had made towards the United hierarchy and coach Erik ten Hag.
However, Ayew said this should not be a distraction for Portugal.
"It is not our problem what is happening within the Portuguese team," he told reporters on Wednesday. "They are all great professionals playing at top teams and they will be ready for the World Cup, whatever else is happening."
Tunisia and Morocco have already managed to hold more fancied European opposition at this World Cup and Ayew said there was no reason why Ghana can't do the same or even better.
"We go into this game with Portugal favourites on paper. But we have to show that it is more important what happens on the pitch. We are playing a big side with top players, but we believe in ourselves and will make it very difficult for them," he said.
"When you are playing the first game of a tournament it is never the decisive one. Whatever happens, you still have a chance to go through.
"The first game is one where you can go for it and be brave. It would be a great bonus for us to get something (from the match)."
LONE SURVIVORS
Ayew and his brother Jordan are the only survivors from the Ghana side that lost 2-1 to Portugal in their final group stage clash in 2014, when Ronaldo scored the winner 10 minutes from fulltime.
"The two teams have changed a lot since then. It is a different game, when we played them in 2014 we had to win by two goals to advance," Ayew said.
"It is not the same game, or the same moment, it is completely different. Every game has its own realities and we will try to give them a tough time.
"We all know in these big tournaments there are surprises that can happen, we just need to be ready. I don’t feel anyone is stressed or has anxiety before the game.
"I am sure when the game comes there will be pressure, if you don't feel it, you are not human."
