Murphy Brown (Candice Bergen) is a recovering alcoholic who returns to the fictional newsmagazine FYI for the first time following a stay at the Betty Ford Clinic residential treatment center. Over 40 and single, she is sharp tongued and hard as nails. In her profession, she is considered one of the boys, having shattered many glass ceilings encountered during her career. Dominating the FYI news magazine, she is portrayed as one of America's hardest-hitting (though not the warmest or more sympathetic) media personalities.

Amid a divided nation, chaotic national discourse and rampant attacks on the press, Murphy decides to return to the airwaves and recruits her FYI team. Joining them is social media director Pat Patel, who is tasked with bringing Murphy and the team into the 21st century.