It has been a starting point for many comedians, award-winning actors, directors, and others in show business, including Del Close, Alan Alda, Alan Arkin, Harold Ramis, Bill Murray, Gilda Radner, John Candy, John Belushi, Dan Aykroyd, Eugene Levy, Catherine O'Hara, Dave Thomas, Chris Farley, Tim Meadows, Colin Mochrie, Ryan Stiles, Mike Myers, Nia Vardalos, Steve Carell, Jordan Peele, Tara Strong, Tina Fey, Amy Poehler, Keegan-Michael Key, Stephen Colbert, Steven Yeun, Cecily Strong, Lauren Ash, Ron Pederson, Ann Pornel, Sam Richardson, Amber Ruffin, Jason Sudeikis, and Aidy Bryant.

On December 16, 1959, The Second City's first revue show premiered at 1842 North Wells Street, with Sills's former wife and Compass Player Barbara Harris singing "Everybody's in the Know".

[6] The cabaret theater comedy style of the Second City tended towards satire and commentary on social norms, and political figures and events.

In 1961, the theater sent a cast to Broadway with the musical revue, From the Second City, directed by Sills and earning Tony Award nominations for ensemble members Severn Darden and Barbara Harris.

A notable criticism came from Second City alumnus Dewayne Perkins, who alleged that the institution initially refused to host a benefit show for Black Lives Matter unless half of the proceeds also went to the Chicago Police Department.

[9] In response to these issues, The Second City instituted changes, including the formation of a steering committee comprising representatives from BIPOC, Latinx, and LGBTQIA+ communities to foster inclusivity and diversity.

The nearly 12,000-square-foot (1,100 m2) entertainment complex at 64 N. 9th Street comprises two cabaret-style live theaters, seven Training Center classrooms, and a full-service restaurant and bar.

Rather than broadcast the usual TV rerun fare, the business, run by the greedy Guy Caballero (Joe Flaherty) sitting in a wheelchair only "for respect," operates a bizarre and humorously incompetent range of cheap local programming.

In-house media melodrama was frequently satirized, including by John Candy, as the vain, bloated variety star character, Johnny La Rue; Thomas's acerbic critic, Bill Needle; Andrea Martin's flamboyant, leopard-skin clad station manager, Mrs. Edith Prickley; Catherine O'Hara's alcoholic, narcissistic, former leading-lady, Lola Heatherton; and Flaherty's effusive talk show host, Sammy Maudlin.

[12] prompting Alexander to apologize and resign, pledging that "The next person to fill the Executive Producer position will be a member of the BIPOC community".

[22] On November 25, 2020, The Second City announced that former Dad's Garage Theatre Company artistic director Jon Carr had been hired as executive producer.

Sixteen alumni have received Jeff Awards for their performances in Second City revues, including David Pasquesi (The Gods Must Be Lazy, 1989), Scott Adsit (Paradigm Lost, 1997), Jackie Hoffman (Disgruntled Employee Picnic, 1993), Shelley Long (Wellsapoppin, 1977), and Nia Vardalos (Whitewater for Chocolate,[25] 1994), with Rachel Dratch and Keegan-Michael Key each being honored twice.

[29] In 2013, the Jeff Awards awarded Best Production: Revue to a Second City show not housed at the venue on Wells Street, The Second City Guide to Opera, a collaboration with the Lyric Opera of Chicago that had been initiated by soprano and Lyric creative consultant Renée Fleming, with Best Director: Revue going to Billy Bungeroth.

Created in 1967 as a way to increase the talent pool, the initial Touring Company, featuring Ramis, Doyle-Murray and Flaherty, was tested on the road for two years before taking the stage as The Next Generation after the mainstage ensemble was sent to perform in New York.

[35] Other notable alumni returning to participate included Steve Carell, Stephen Colbert, Jeff Garlin, Jack McBrayer, James Belushi, Dan Castellaneta, Amy Sedaris, Ian Gomez, Richard Kind, Robert Klein, Fred Willard, David Rasche, Betty Thomas, and George Wendt,[36] as well as original cast member Mina Kolb, Compass Player Shelley Berman, and co-founder Bernard Sahlins, along with Playwrights Theater Club co-founder Sheldon Patinkin;[37] he later served as assistant director to Paul Sills, then succeeded him as artistic director, spending over five decades as an artistic mentor of the troupe while chairman of the theater department at Columbia College Chicago for three decades.

The Training Centers have grown substantially since the Second City Conservatory was established in the mid-1980s under the tutelage of longtime Chicago improv instructors and mentors Martin de Maat and Sheldon Patinkin.

Former Training Center students include Steve Carell, Tina Fey, Amy Poehler, Mike Myers, Chris Farley, Tim Meadows, Bonnie Hunt, Stephen Colbert, Halle Berry, Sean Hayes, Amy Sedaris, Jon Favreau, Hinton Battle, Jack McBrayer, Dave Foley, and Kevin McDonald.