The series is set in a New York City news radio station, WNYX, and starts with the arrival of a new news director, Dave Nelson (played by Dave Foley). He finds a staff with often weird habits.
The station is led by multi-millionaire Jimmy James (Stephen Root), who often places strange bets with his rich friends and is desperately looking for a wife. Secretary to Dave is the extravagantly dressed Beth (Vicki Lewis), whose work mainly consists of eavesdropping. The station's anchorman is the ego-centric Bill McNeal (Phil Hartman), with Catherine Duke (Khandi Alexander) at his side. Reporters are the clumsy and not very bright Matthew Brock (Andy Dick) and the ambitious and intelligent Lisa Miller (Maura Tierney), with whom Dave has a relationship. Joe Garelli (Joe Rogan) is the station's electrician, who builds everything he needs by himself.
In addition to the often strange habits of the staff, the series also contained two finales far removed from the rest of the series, the first of which demonstrated what NewsRadio would be like if it were to occur in space. The second was a parody of Titantic.
After Phil Hartman was killed in 1998, he was replaced by Jon Lovitz, playing Max Louis.