Inspired by The Decameron and its dark and satirical novellas, Boccaccio in the Berkshires chronicles the foibles of seven women and three men, all in their twenties, who meet in an online chat room for asymptomatic pandemic survivors. They have all endured the deaths of loved ones and decide to shelter together for fourteen days in an Italianate mansion in the Berkshires, offered to the group rent-free. The vacant but furnished villa provides a luxurious, yet bizarre, setting for members of the chat room, who leave their homes in different cities around the United States.

Over the course of their stay, they bond together in unexpected ways as they tell each other stories, ranging from the personal to the ludicrous, at times riffing on the absurdity of Boccaccio's tales. A terrible storm fractures the group and forces the characters to come to terms with their own lives as they pursue love, faith, and the truth that medieval history ultimately reveals.