Pokémon Black and White are role-playing video games with adventure elements, presented in a third-person, overhead perspective. There are three basic screens: an overworld, in which the player navigates the main character; a battle screen; and the menu, in which the player configures their party, items, or gameplay settings. The player controls a Pokémon Trainer who begins the game with a single Pokémon and is able to capture more using Poké Balls.  Like all other Trainers, the player can carry up to six Pokémon at one time. However, the game also includes a network of PCs to store hundreds of Pokémon. PCs are found in certain buildings—named, "Pokémon Centers", where the player can heal their Pokémon when they have low health or have fainted.

Pokémon can learn up to four moves, including attacking moves, healing moves, and moves that inflict status conditions on the opponent. They have six stats that affect battle performance: maximum hit points (HP), Attack, Defense, Special Attack, Special Defense, and Speed. Attack and Special Attack are distinguished from Defense and Special Defense by the types of moves being considered: generally, moves involving physical exertion are physical, while moves involving supernatural or elemental powers are special. Moves are classed as one of seventeen types: Normal, Water, Grass, Fire, Electric, Ghost, Bug, Fighting, Ice, Steel, Rock, Poison, Psychic, Dark, Dragon, Ground, and Flying; Pokémon can have one or two types. Generally, most of a Pokémon's moves correspond to its typing. A Pokémon's type makes it vulnerable or resistant to others; for example, Fire-type Pokémon are weak to Water-type moves, while Grass-type moves do little damage to them and Electric-type moves do normal damage.

When the player encounters a wild Pokémon or is challenged by another Trainer to a battle, the screen switches to a turn-based battle screen where the Pokémon fight. During the battle, the player may use a move, use an item, switch the active Pokémon, or flee. However, the player cannot flee a battle against another Trainer or against certain wild Pokémon that are stronger than the player's. When a Pokémon's HP is reduced to zero, it faints until it is revived. If an opposing Pokémon faints, all of the player's Pokémon who participated in defeating it receive experience points. After accumulating enough experience points, a Pokémon may level up, increasing its stats. Many Pokémon evolve into other forms after certain conditions are met, usually after reaching a certain level threshold or by having a certain item used on them.  At the "Day Care" location, the player can breed two of their Pokémon—usually, a male and a female—to create Eggs that hatch into baby Pokémon at level 1.

Pokémon Black and White takes place in the Unova region, based on New York City. As with all regions, Unova consists of a number of cities and towns connected by "Routes". Random encounters may take place in tall grass along routes or in bodies of water. The player occasionally battles Trainers in cities and towns, as well as along routes. In addition, eight of the game's cities and towns are homes to "Gym Leaders", powerful Trainers specializing in certain types of Pokémon; beating a Gym Leader gives the player a "Badge". All eight Badges are needed to unlock the Pokémon League, where the player faces off against the "Elite Four" and, finally, the Champion. Across Unova, items can be found on the ground or purchased from "Poké Marts".