Set in the titular city in the 16th century, Venice lets players take the role of wealthy, influential merchants as they ride their gondolas up and down the city's canals, train their assistants, complete contracts, and leverage their influence to gain political power. But business is anything but usual. As they broker contracts and flirt with crime, merchants must avoid arousing the suspicion of the Venetian Inquisition, lest they find themselves arrested and their businesses shut down.

In the game, players move their two gondolas around the board. When they move a gondola, they may activate the assistants they have placed previously on any building they pass, but they may train (and improve the capabilities of) only the one on which they end their movement. Assistants allow you to gain resources, trade, make money, and take an array of other actions depending on the buildings to which they are assigned. When resources are made, they are placed in the gondola, and these will be used to fulfill lucrative contracts.

Space is limited on the city's canals, however, and each time you pass another merchant's boat, gossip will spread, raising your suspicion level with the Inquisition. Lower your suspicion with visits and donations to the church, or academic institutions - or throw caution to the wind and engage in unsavory activities for money or information. During the game, being such a well-known merchant can be a boon to your political career, but at game end, the most suspicious player will be made an example of by the Inquisition - blocking your victory even if you have the most points.