The game completely abandons the idea of previous titles that the playfield is being pushed down by some sort of mechanical device and instead attaches groups of bubbles to nodes that move downwards. When a node is no longer connected to any bubbles it will disappear and when all nodes in a level have vanished the level is complete. One result of this change that may appear strange to players of previous versions is that shooting a bubble to the top of the visible playfield without striking any bubbles causes it to bounce and start travelling back downwards. The player is not penalised if such bubbles again leave the playing field without attaching to anything (except for adding to the number of moves until the field is pushed down by one empty line). Despite this some versions include a reimplementation of the Puzzle Bobble 2 levels now built around nodes (entitled Version 2.5).

Gameplay is further varied by the implementation of new scrolling playfields that are several times as high as the screen and must be conquered as an endurance event. Each scrolling playfield occupies the same space on the world map as five previous levels.

This game also marks the introduction of rainbow bubbles into the series - bubbles that are initially transparent and filled with a rainbow. Any adjoining bubble that is burst, the rainbow bubbles next to them switch to the colour of the burst bubble, allowing the player to build up chain reactions.

The ability to choose a character was introduced, but only to the VS Computer mode. As in Bubble Bobble, the 1st player, when he/she picks Bub, gets Bub, and the 2nd player gets Bob. In the Nintendo 64 version, a 4 player simultaneous option is available.