Version differences

The PlayStation 3, Wii and Xbox 360 versions of the game are fast-paced platformers with some puzzle scenarios and plays similar to LEGO Indiana Jones: The Original Adventures, but can be finished in about an hour or two. The Wii version is slightly different than the PlayStation 3 and Xbox 360 versions in that it uses more artfully rendered visuals to accommodate that system's graphical constraints (for example, rocks have purplish textures and the sky is represented with a cartoony skybox in the Wii version, while rocks have brownish, more realistic textures and the sky is represented by a fluid skydome in the PlayStation 3 and Xbox 360 versions). The Wii version also supports optional motion controls to perform certain actions, such as shaking the Wii Remote to launch rocks as missiles or tilting it down to reach over ledges to help a partner up. Carl and Russell can also use special abilities for a limited number of times to scare off or distract enemies or bosses, accessed by pressing certain directions of the directional pad. Cutscenes are presented in newsreel format, similar to Spotlight on Adventure in the film's first scene. Character health is measured discretely in these versions, and the characters' survivability gradually increases automatically as the game progresses. These versions also have the fewest bosses, which are simply a giant anaconda, a crocodile, and The Spirit of Adventure, Muntz's airship. There are two biplane sequences, one at the start of the game that takes place immediately before a final battle over Paradise Falls, and another for the actual battle, and in both of them, a second player can "man the guns" and fire at incoming enemies and ground artillery with an on-screen reticule, while sharing the first player's camera view. This feature also takes advantage of the Wii Remote pointer in the Wii version to control Player 2's reticule. Loading screens in these versions also displays hints and trivia about the real wildlife near the tepui.

The Microsoft Windows, Mac OS X, PlayStation 2 and PlayStation Portable versions of the game are longer, giving the player more opportunities to explore the various terrain atop the tepui as the characters take longer detours to reach their destination. At the beginning of these versions, the player is exclusively required to stop the house from floating away. These versions also exclusively feature side areas that cannot be accessed the first time around without acquiring a certain tool, as well as fast-moving linear levels (namely on-rails chase sequences played from a reverse angle or river canoeing courses), where players cannot backtrack and must carefully avoid accidents that instantly require a restart from a checkpoint. Health is measured in a continuous gauge. There are four bosses in these versions, which are three battles against some of Muntz's top dogs, along with The Spirit of Adventure.

The Nintendo DS version is only six levels long, but they usually consist of one or more large areas and players are required to have Carl and Russell together at the end of each level (and at the end of each part of some levels), which becomes a challenge as the characters are easily separated in this version. There is also a boss at the end of each level. Exclusively in this version, players must acquire and use certain tools to overcome obstacles (although the use of such tools is constrained by an energy meter), and are encouraged to finish levels as fast as possible, but must be careful not to arouse too much suspicion from Muntz's dogs, who patrol the jungle and will engage Carl and Russell in battle if they move around too often. A special time attack mode is available for each level that unlocks rare bugs for a collection. Characters also share a continuous health bar as in the Microsoft Windows, PlayStation 2 and PlayStation Portable versions, although total loss of health would require a full restart of the current level due to a lack of checkpoints. However, levels that are divided into multiple sections offer a fresh spring in between areas that can fully replenish health and a checkpoint is available at the start of each boss battle. In between levels, players are taken to a campsite where they can purchase health upgrades and consumable supplies for power-ups, examine acquired tools, save progress and more. Some sequences involve using touch screen gestures, such as pulling a lever to extend a bridge, turning a crank to operate an elevator or repeatedly scribbling on the screen to break free of traps. This version also exclusively has mini-games that can be played with a friend who has a copy of the game.