Chicago Hope is part of the Tommy Westphall Universe, a shared fictional universe theory connecting numerous TV series through crossovers and references.

Fyvush Finkel and Kathy Baker appeared as their Picket Fences characters in the first season, while Mandy Patinkin and Héctor Elizondo brought their Chicago Hope characters to Picket Fences that same year.

Mandy Patinkin appeared uncredited as Dr. Geiger in a 1995 episode of NBC's Homicide: Life on the Street, footage shot by Chicago Hope producer John Tinker as a favor to his St. Elsewhere colleague Tom Fontana.

Chicago Hope characters crossed over early into the show Early Edition, with Rocky Carroll, Jayne Brook, and Héctor Elizondo guest-starring in scenes set in the hospital.

With the exception of a few on-location scenes, the vast majority of Chicago Hope was filmed on sound stages at the Twentieth Century-Fox studios in Century City, Los Angeles.

On November 18, 1998, Chicago Hope became the first regular series episode ever broadcast in HDTV, with the episode titled 'The Other Cheek'.

The series broke a network television taboo by showing a teenager's breast after her character underwent reconstructive surgery, a scene that went relatively uncriticized due to its medical context.

Mark Harmon's character said the word 'shit' during a trauma scene, which drew little criticism but inspired the South Park episode 'It Hits the Fan'.

Mark Harmon, Rocky Carroll, and Lauren Holly, all former Chicago Hope cast members, later starred together in NCIS starting in 2008.

Thomas Gibson later starred alongside Mandy Patinkin in Criminal Minds, a series that also featured Shemar Moore, who had guest-starred on Chicago Hope during Season 4.