Located in Lucille Ball’s hometown of Jamestown, New York, the museum opened in August 2018 and reported 66,000 visitors in its first year of operation.

Entertainment companies have provided items from their archives, including Desilu Too, NBC Universal, Paramount Pictures, and Warner Brothers.

[10] Additionally, the center's advisory board includes members of the comedy industry, including Carl Reiner (2018-2020), Lewis Black, Paula Poundstone, W. Kamau Bell, George Schlatter, Laraine Newman, Jim Gaffigan, Pete Docter, Kelly Carlin, George Shapiro (succeeded by Amy Poehler after Shapiro's death),[11] Rain Pryor, Paul Feig, Kitty Bruce, Robert Klein, David Steinberg, Violet Ramis Stiel, Mark Russell, Alan Zweibel, Robin Zweibel, Paul Provenza, Joan Dangerfield, Jeff Abraham, and Stephen J. Morrison.

[12] In August 2019, the National Comedy Center was named one of the "World's Greatest Places"—one of "100 new and newly noteworthy destinations to experience right now" and one of only nine attractions to visit in the United States—by TIME magazine.

Its educational programming on the art form has featured Tiffany Haddish, George Lopez, Margaret Cho, Norman Lear, Rain Pryor (daughter of Richard Pryor), Jay Leno, Kenan Thompson, Gabriel Iglesias, Jimmy Fallon, Lin-Manuel Miranda, "Weird Al" Yankovic, and many more.