Like other collectible card games, players play one versus one to reduce their opponent's health to zero.

The fictional universe of Runeterra, released by the developer through short stories, comic books, and an animated series, provides flavor and theming for the game's cards.

Legends of Runeterra has been well received by critics, who point to its generous progression systems, accessible gameplay, and high-quality visuals, and has won several industry awards.

This is reflected visually on each players' half of the board, with a sword icon representing attack or a shield for defense.

[7] Unit cards, which includes champions and non-champions (followers), have a number representing their attack and health statistic; attack is how much damage a unit deals to either the Nexus or its blocker, while health reflects the maximum damage a card can take before being removed from play.

[6] A fourth speed, Focus, resolves immediately and does not pass over turn priority, but can only be used outside of combat.

[13] Landmarks are played with regular unit mana and consume a position on the player's board; they cannot block or attack.

[16] Riot recruited professional Magic competitors as early playtesters; of them, Steve Rubin was invited to return permanently and later moved into the design team.

[16] Accessibility was a priority for the developers, who sought to provide a familiar experience while not forcing players to buy booster packs, a random bundle of cards otherwise common in the CCG genre.

[16] In 2023, an update introducing an Emporium, in which cards and cosmetic items could be purchased with real currency, was released.

The Emporium was criticized for its pricing and bugs, with director Dave Guskin acknowledging the issues.

[24][25] Eurogamer observed the unusual timing of the reveal, given the recent failure of Valve's Artifact and the waning audience for Blizzard Entertainment's Hearthstone.

[31] The official launch also brought a new set to the game, Rising Tides, introducing 120 new cards and a new region—Bilgewater.

[33] Call of the Mountain introduced the region of Mount Targon and was released for PC and mobile devices on August 26, 2020.

[35] The tenth and final region of the game, Bandle City, was released on August 25, 2021,[36] and brought four expansions instead of the usual three.

Giving the game an 85/100, Steven Messner, writing for PC Gamer noted the absence of "booster packs", bundles of cards purchasable with real currency, having been replaced with a generous battle pass system which gives out an abundance of free cards and crafting material every week.