Produced by Paramount Television, the series updates the world of Nero Wolfe to contemporary New York City and draws few of its stories from the Stout originals.

Nero Wolfe (William Conrad) enjoys a life of refined self-indulgence in his comfortable Manhattan brownstone — reading, dining, spending regular hours in his rooftop plant rooms, and only reluctantly involving himself in the detection of crime.

Famously sedentary, Wolfe relies on his legman Archie Goodwin (Lee Horsley) to collect the clues and the suspects in any case at hand, while he spars with his live-in chef Fritz Brenner (George Voskovec) and bickers with his resident orchid nurse Theodore Horstmann (Robert Coote, in his final role).

In March 1980, Nero Wolfe was one of half-a-dozen new series being considered by the team of Brandon Tartikoff and Fred Silverman at NBC, according to Peter Boyer of the Associated Press.

"[8] In December 1980, NBC announced that Nero Wolfe would begin airing in January 1981, as "an ideal alternative to the competition in this time period" — The Dukes of Hazzard.

Horsley spoke of his love for Rex Stout's books and characters, and credited the care taken with the production's art direction, set design and wardrobe in creating the atmosphere of the stories.

[12] The plant rooms were stocked by Zuma Canyon Orchids of Malibu, California, which on the eve of the series registered the hybrid Phalaenopsis Nero Wolfe with the Royal Horticultural Society.

[16] In April 1996, when the TV Land network made its debut, Nero Wolfe was featured in its "Saturday Cavalcade" lineup of great detectives.

[17] In 1999 the series was part of an afternoon block of TV Land's counterprogramming to network soap operas, and it also aired in the wee hours of the morning.