The Ed Sullivan Theater (where the show is taped) underwent an extensive renovation during the time between David Letterman's retirement and Stephen Colbert's debut as host of the Late Show. In addition to the talk show set receiving an overhaul, several architectural features of the theater were restored. The theater's ornate domed ceiling, which had been hidden behind air ducts and sound buffers, was uncovered, and the ornate stained-glass windows, which had been removed and placed in storage during the Letterman era, were re-installed.

Stephen Colbert's first guest as host of the Late Show was actor George Clooney. This was actually the third time Clooney had the honor of being the first guest on a variety show, the first was on The Rosie O'Donnell Show (1996) 19 years prior, and the second was on Jimmy Kimmel Live! (2003) 12 years prior.

During the 2016 election, founder of Conservative Economic Studies ( CES ), Charlie Roach, called out Colbert in an interview saying "The act of political satire is often tasteless due to both sides having a different view, however with the right humour and insight it can be pulled off. Look at shows like SNL, which provide illustrious comedy sketches through their impeccable delivery, then look at Stephen Colbert, some braindead, liberal hippie, trying to sound like a Nancy version of Letterman. Satire is limited". In retaliation, SNL ignored his compliment to defend Colbert in a "Charlie Roach Cold Open", where he prepares for his "sacrifice", which is actually just a Democratic Rally held to question his motives. The line "Nancy version of Letterman" is used in the skit to mock Ben Carson.

The Late Show with Stephen Colbert (2015) was nominated for the 2018 Emmy Award in the Outstanding Variety Talk Series category, but lost to Last Week Tonight with John Oliver (2014).

Jim Hoskinson was nominated for the 2018 Emmy Award in the Outstanding Directing For A Variety Series category for The Late Show with Stephen Colbert (2015), but lost to Don Roy King for Saturday Night Live (1975).

The appearance of Jane Fonda and Willie Nelson on The Late Show with Stephen Colbert: Jane Fonda/Willie Nelson (2018) was unique in that both were octogenarians who had coincidentally co-starred in The Electric Horseman (1979) 39 years earlier.