Matthew Perry and Thomas Lennon previously starred together as mismatched best friends in 17 Again (2009).

Lauren Graham plays Gaby, Oscar's ex wife. Matthew Perry and Lauren Graham are very good friends and dated briefly in the past. She also appeared in Go On (2012), in which Matthew Perry starred too. Graham also had a guest spot on Studio 60 on the Sunset Strip in which Matthew Perry's character asks her out, and she accepts, albeit unwillingly.

Matthew Perry and the cast of Friends (1994) vocalize the original theme song for The Odd Couple (1970) TV series in Friends: The One with the Dozen Lasagnas (1995).

Thomas Lennon guest starred on Friends, episode, "Friends: The One in Vegas: Part 1 (1999)," as Randall, Joey's hand twin.

Oscar's (Matthew Perry) first line to a radio caller in The Odd Couple (2015) is the same first line from the premiere of Go On (2012), in which he also starred.

Thomas Lennon appears on How I Met Your Mother (2005) as Claus, in which at one point during season 8, he watches a show very similar to The Odd Couple (2015), but in German. He points out that one roommate is "neat" and the other is "very, very neat."

Garry Marshall, who is the creator of the original series (The Odd Couple (1970)) and served as consultant on this version, also plays Oscar's dad, died on July 19, 2016 . On the wall in Oscar's apartment is a photo of Oscar (Matthew Perry), Felix (Thomas Lennon), and dad, Garry as tribute to him.

Christine Woods plays Ashley, Felix's ex wife. She also played Matthew Perry's former (deceased) wife in Go On (2012).

The sports bar that the characters frequent is called Langford's. Matthew Perry's middle name is Langford.

Oscar's (Matthew Perry) apartment is the same set as used for Frasier's apartment in Frasier (1993), although totally refurbished. Also of interest is the fact that at one point on Frasier, Martin (Frasier's dad) moves in and is living with Frasier which is somewhat like The Odd Couple (2015) but with the roles reversed.

Of all of the Odd Couple presentations, for film or television, the actors playing the Felix Unger character have always had top billing. This particular series is the first time the actor playing Oscar Madison has top billing.

Joey and Chandler (Matthew Perry) had a poster of the original Odd Couple up in their apartment in Friends.

Lindsay Sloane and Wendell Pierce have previously worked together in Horrible Bosses (2011). Jennifer Aniston, who starred along with Matthew Perry in Friends (1994), has worked on that movie too.

Thomas Lennon (Felix) and Lindsay Sloane (Emily) both appeared in How I Met Your Mother (2005).