Before the series, Culp had written a pilot script in which he would play a James Bond-type American spy. He showed the script to Carl Reiner who then recommended him to Sheldon Leonard. The script was eventually produced as the episode "The Tiger".
The first American dramatic TV series to feature a black actor in a lead role. Scripts were peppered with unique lingo. One catchphrase, "wonderfulness," became popular and was later used by Bill Cosby for the title of one of his comedy albums.
Bill Cosby's character, Alexander Scott, was originally intended to be an older mentor to Robert Culp's trainee agent, Kelly Robinson. Executive producer Sheldon Leonard cast Cosby in the role after seeing one of his routines (Scott was originally intended to be a Caucasian). Due to this casting change, the writers thought an occasional reference to Cosby's race would be a necessity, given the tumult of the times. In an early episode, "Danny Was a Million Laughs", guest star Martin Landau's character makes a racial joke at Scott's expense. Culp and Cosby demanded that no more racial jokes be done, and none were for the run of the series.
The show was not aired on certain NBC affiliates in the south due to the fact that it dared to show an African-American actor (Bill Cosby) on the same level as a white actor (Robert Culp). This also included the original Star Trek series where a black actress (Nichelle Nichols) and Asian actor (George Takei) are seen as part of the U.S.S. Enterprise's crew.
The series' ratings declined in the third season. This was due to a timeslot change from Wednesday nights to Monday nights where it was against The Carol Burnett Show (1967). NBC offered executive producer Sheldon Leonard the choice of having the series renewed or making a new series. Leonard decided to produce My Friend Tony (1969) instead. He believed that continuing "I Spy" would lessen its syndication value as the series was struggling with creating new ideas. Also, NBC had refused to move the show back to Wednesdays. Culp and Cosby had tired of the series and were relieved that it was cancelled.