Legends of Runeterra offers a variety of cards to allow each player to play games in their own unique way. A deck of cards must consist of no more than 6 champion cards (allowing for 3 different champions to be present), 2 regions, and 40 cards total.

Legends of Runeterra is played one against one. Each player begins the match with a hand of four playing cards randomly selected from their card deck, a 20-health-point nexus, and zero mana. Before the match begins, each player also has the option to trade out any of the first four cards they drew for random different ones from their deck.

In order to play cards, players must spend mana gems. There are three types of cards: Champions, Followers, and spells. Champions are the most powerful cards in the game, and each have a criterion that, once met, will level up the card to a more powerful version. Followers consist of all other normal playable cards and spells cause effects when played.