Isthmus takes its name from the land mass that forms the heart of Madison's downtown and houses the twin engines of the city's economy, the University of Wisconsin—Madison and the Wisconsin State Capitol.

On March 19, 2020, Red Card ceased Isthmus' print publications for the first time in forty years due to the COVID-19 pandemic and laid off the newspaper's entire staff.

[7] Red Card retained ownership of Beer and Cheese Fest, Paddle and Portage, and other events created under the Isthmus brand.

Dylan Brogan, Judith Davidoff, Linda Falkenstein, and Bob Koch led the transition to a nonprofit model and worked as volunteers for months to save the paper during the height of the COVID-19 outbreak.

Isthmus, through both its print edition and its website (Isthmus.com), carries investigative and in-depth articles, offers opinions and commentaries on current events, provides incisive coverage of the arts, and features stories on trends and culture in the Madison area.