The player no longer starts in Nuvema Town, instead starting in Aspertia City.
Instead of the usual 5 Poké Balls, the player is given 10 at the start of his or her journey.
Chili, Cress, Cilan, Lenora and Brycen are replaced by Cheren, Roxie and Marlon as Gym Leaders.
Bianca gives the player a Starter Pokémon.
A new Team Plasma has formed, and is run by Ghetsis.
Colress, a Team Plasma member, is battled frequently throughout the story.
Rood, Zinzolin and the Shadow Triad are battled as part of the story.
The Gym Leader order has changed to Cheren, Roxie, Burgh, Elesa, Clay, Skyla, Drayden, Marlon.
Iris is the new Champion of Unova.
Ghetsis returns and plans to freeze Unova with Kyurem.
N returns to Unova with either ZekromB2 or ReshiramW2, who is then fused with Kyurem to form either Black KyuremB2 or White KyuremW2.
Unlike Pokémon Black and White, the version mascots Black KyuremB2 or White KyuremW2 can't be caught within the story, but can be obtained post-game by following certain requirements.
Cobalion and Virizion interact with the player, making it possible to catch them during the storyline, although it is possible to catch all three Pokémon including Terrakion.
Several tag battles take place throughout the game: one with the other player character, two with Cheren, four with Hugh, one with Bianca, and a daily tag battle with one of either Chili, Cress, or Cilan against the other two brothers.
A new attraction known as the Pokémon World Tournament opens up in Driftveil City, where the player battles Gym Leaders and Champions from all five regions, among others.
Another new attraction introduced is the Pokéstar Studios, located in Virbank City, where the player takes part in many different movies. Brycen and Sabrina appear here.
Lenora revives the player's fossils.
Several new key items exclusive to Black and White 2 are introduced.
During the post-game, the player may find N at his castle and on the first visit, battles his ZekromB2 or ReshiramW2, who is free for capture after defeating N. Subsequent battles can be done once a season and feature N using a team of Pokémon centered around that season.
Several areas that were previously accessible in the post-game of Black and White are now part of the main story. In contrast, some of the areas that were formerly part of the main story are now found in the post-game.