Lewis & Clark is a board game in which each player manages an expedition with the goal of crossing the North American continent. Their goal is to be the first to reach the Pacific Ocean. Each player has their own Exploration Corps that will be supplemented by the Native Americans and fur traders they meet along their journey. They must manage their characters and the resources they find along the way wisely. But beware, sometimes frugality is better than abundance.

Lewis & Clark uses cards with multiple functions. To be activated, one card must be combined with another card, which will then be temporarily unavailable. As a result, players are constantly faced with a dilemma: play a card or sacrifice it. Throughout the game, players acquire character cards that expand their hand, building a crew that gives them more options, but this must be optimized as they will recycle their cards more slowly. This new "hand building" mechanism fits well with the historical context.

Since the aim of the game is to be the first to reach the coast of the Pacific Ocean, the timing and use of the other players' positions are crucial.