"Ты знаешь, как играть в эту игру?"
Translation:Do you know how to play this game?
играть в + Accusative is used with games
играть на + Prepositional is used with musical instruments.
Also, играть + Accusative is used to express which character an actor plays.
When you say "знаю, как играть (делать, водить (driving) and other verbs) it means that you know how theoretically to do it. If you say "умею играть (делать etc)" - it means that you have had experince in it.