Play begins in pai gow poker by making a wager. Next everyone receives seven cards. A roll of the dice or a randomly generated number determines which player gets the first set of cards. The pai gow poker players then each arrange their seven cards into a five-card hand and a two-card hand. The five-card hand is ranked as in poker, with the exception that an A-2-3-4-5 straight is the second highest straight. The two-card hand will either be a pair or two individual cards. The highest two-card hand is a pair of aces and the lowest is a 2-3.

After all the pai gow poker players have arranged their hands the banker arranges theirs according to a set of fixed rules known as the pai gow poker "house way." Then the pai gow poker player's five-card hand is compared to the dealer's five-card hand. Likewise the pai gow poker player's two-card hand is compared to the dealer's two-card hand. The highest hand wins. In the event of an exact match between hands, called a copy, the tie goes to the banker. If the pai gow poker player beats the dealer with both hands the player wins even money, less a 5% commission. If the pai gow poker player wins one and loses one the bet is a push. If the pai gow poker player loses both the player loses the entire wager.

When setting the hands the two-card hand may not be higher then the five-card hand in pai gow poker. If it is then both hands are deemed "foul" and both lose. The joker can only be used to complete a straight, flush, or straight flush, otherwise it is treated as an ace. At some places if there is an empty seat the dealer will also deal a "dragon" hand in pai gow poker. Another player may assume the pai gow poker dragon hand if they wish, essentially playing two positions rather than one. The player may have to use the pai gow poker house way in setting the dragon hand.

In pai gow poker any player may elect to be the banker in turn. If a player banks the 5% commission is charged on the net win. When a player is the banker the dealer will still play, betting an amount equal to the last bet the player made when the dealer was banking. It is strongly to the advantage of the player to be the banker as much as possible in pai gow poker because the dealer wins on copies and the 5% commission is charged after losses are set against winnings.

The opportunity to bank in pai gow poker usually rotates from person to person, including the house, but sometimes will zigzag between the players and the dealer. If the player wants to bank they must have enough money on the table to pay off all winning bets of the other players and dealer. The player must also have played a previous hand against the pai gow poker house banker to bank. Some casinos will allow the player to co-bank with the house. If this option is elected the casino will assume half the financial responsibility of the outcome. The player must set their hand according to the pai gow poker house way if co-banking.