In Lewis & Clark, each player leads their own "Corps of Discovery" across the continent. His team will be completed by the Indians and trappers encountered along the trip.

The players lead an expedition across the North American continent. The goal is to be the first to reach the West Coast. Lewis & Clark is therefore a racing game. Only the first place counts.

Each player has in their hand Character cards that form their expedition. These characters allow you to perform actions such as gathering resources, moving forward on the course, asking for help from the Indians. To be triggered, the action corresponding to a card must be associated with a Force which is provided by either another card or by Indians.

On each game turn, a player must perform an action. He can also recruit a new Character and thus improve his hand of cards. Finally, regularly, players will be able to establish their Camp in order to regain control of the cards played previously. While in Encampment, the expedition's load of resources and the number of Indians hosted can eventually lose the hard-earned lead. Appropriate management of resources and Indians is therefore crucial in the game.

The game ends immediately as soon as a player has moved their Camp to or beyond Fort Clatsop.