Released in Japan on September 21, 2000; in North America on December 4, 2000; and in PAL regions on June 15, 2001, it is the second Pokémon-themed entry in the Puzzle League series.

In competitive modes, players can perform combos and/or chain clears to cause objects called garbage blocks to fall on their opponent's grid, further filling it in an attempt to cause them to lose.

Using a Game Link Cable, two players can compete in standard versus play, Time Zone, or Line Clear.

At the start of the game, players only have access to Chikorita, Cyndaquil, and Totodile, but can unlock six more Pokémon by completing specific objectives in Challenge mode then defeating their trainer.

[1] In a preview, IGN praised Pokémon Puzzle Challenge for its gameplay, calling them "nice and simple to appeal to players of all ages and levels".

[15][16] Nintendo Power also listed Pokémon Puzzle Challenge as the 13th best Game Boy/Game Boy Color video game, calling the gameplay only second in addictiveness to Tetris, ultimately giving the nod to this version of the gameplay over Tetris Attack because of a few extra features.

[19] IGN editor Craig Harris called the return of the Tetris Attack gameplay "welcome", commenting that it was "as fun and addictive as it ever was".

[20] In a Pokémon video game retrospective, fellow IGN editor Lucas M. Thomas commented that while it didn't bring anything new to the Tetris Attack gameplay, it being in a "new, Colorized portable version was enough".

[21] GameSpot editor Frank Provo commented that it "does the Pokémon license proud", calling it both "addictive" and praising its overall value.

[23] William Schiffmann of the Associated Press commented that while it doesn't "break any new ground" and the Pokémon theme constitutes a "sales gimmick", fans of Tetris would enjoy it.