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

Each player has in hand Character cards that make shipment. These characters can perform actions such as harvesting resources, progress on the course, seek the help of the Indians. To be triggered, the action corresponding to a card must be associated with a force that is provided by either another card or by Indians.

At each turn, a player must perform an action. It can also recruit a new character and improve his hand of cards. Finally, regular players can establish their camp to regain control of the previously played cards. During the Camp, the loading of the consignment and the number of resources allowed Indians may possibly lose the hard-won advance. A proper management of resources and Indians is crucial in the game

The game ends immediately when a player has brought his camp on or beyond Fort Clatsop.