The aim of the game is to be the first player to score 500 points, achieved (usually over several rounds of play) by being the first to play all of one's own cards and scoring points for the cards still held by the other players.

Uno includes 108 cards: 25 in each of four color suits (red, yellow, green, blue), each suit consisting of one zero, two each of 1 through 9, and two each of the action cards "Skip", "Draw Two", and "Reverse". The deck also contains four "Wild" cards and four "Wild Draw Four".[6] Sets manufactured since 2018 include 112 cards, adding one "Wild Shuffle Hands" and three customizable Wild cards.[2]

For each hand, a dealer is determined by having each player randomly draw one card from the deck. The player with the highest number card deals, and all cards are reshuffled into the deck to begin the dealing.

To start a hand, seven cards are dealt to each player, and the top card of the remaining deck is flipped over and set aside to begin the discard pile. The player to the dealer's left plays first unless the first card on the discard pile is an action or Wild card (see below). On a player's turn, they must do one of the following:

• play one card matching the discard in color, number, or symbol
• play a Wild card, or a Wild Draw Four card if allowed to (see restrictions below)
• draw the top card from the deck, and optionally play it if possible

Cards are played by laying them face-up on top of the discard pile. Play initially proceeds clockwise around the table.

Action or Wild cards have the following effects:

• A player who draws a card from the deck must choose whether to play that card immediately or keep it. No cards already in their hand may be played on that turn.
• A Wild card may be played on any turn, even if the player holding it has cards that will match the current color, number, and/or symbol.
• A Wild Draw Four card may only be played if the player holding it has no cards matching the current color. The player may have cards of a different color matching the current number/symbol or a Wild card and still play the Wild Draw Four card.[6] A player who plays a Wild Draw Four may be challenged by the next player in sequence (see Penalties) to prove that their hand meets this condition. An illegally played Wild Draw Four card incurs no penalty for its user unless challenged.
• A player using a Wild or Wild Draw Four card must declare the new matching color before ending their turn, and may declare the current color if desired.
• If the draw deck runs out during play, the top discard is set aside and the rest of the pile is shuffled to create a new deck. Play then proceeds normally.
• It is illegal to trade cards of any sort with any other player at any time.

A player who plays their penultimate card must call "Uno" as a warning to the other players.[7]

The first player to get rid of their last card ("going out") wins the hand and scores points for the cards held by each other player. Number cards count their face value, all action cards count 20, and Wild and Wild Draw Four cards count 50. If a Draw Two or Wild Draw Four card is played to go out, the next player in the sequence must draw the appropriate number of cards before the score is tallied.

The first player to score 500 points wins the game.