Each Anno Domini set consists of 340 cards, with a description of a historical event on one side of the card and the year (and sometimes specific date) in which it happened on the other. Anno Domini: Wissenschaft & Forschung focuses on historical events related to science and research. Like all Anno Domini sets, this game can be played as a standalone or mixed with some or even all editions.

In Anno Domini: Wissenschaft & Forschung, each player receives nine cards (or fewer, if you want the game to be shorter) and may look only at the descriptions. In turn, players place a card on the table, trying to place their card in chronological order to those already present. Instead of adding a card, a player may claim that the order in which the cards have been placed is incorrect. In this case all cards are turned over and the correct years revealed.

If the order is correct, then the doubting player receives two cards and skips a turn. If the order is incorrect, then the previous player – who accepted the order as correct or made it incorrect through her own placement – receives three cards. The first player with no cards remaining in hand wins.