One of the running series jokes was Murphy Brown's inability to get a good secretary or one that could work with her. During the show's 10-year run, Murphy had a total of 93 secretaries. (They were referred to by number in the closing credits cast list, as "Secretary #1," "Secretary #2," etc.) One that was very efficient was Marcia Wallace, playing her Carol Kester character from The Bob Newhart Show (1972). At the end of the show, Bob Hartley (Bob Newhart) showed up and pleaded for her to return, which she did. In one episode, Murphy discovered there was a support group for her former secretaries, where they comforted each other over their inability to keep the job.

After receiving her 5th Emmy Award for the role of "Murphy Brown", Candice Bergen declined all future nominations for that role.

The outside building shown as Murphy Brown's home is the same building used to show as the home of Diana Prince in Wonder Woman (1975).

The recurring character of Stuart Best (played by Wallace Shawn) is a reference to former Beatles members Stuart Sutcliffe and Pete Best.

In the final episode of season four, Murphy Brown gave birth to her child, Avery. Around that time Vice President Dan Quayle, during a televised debate, criticized the show for introducing the theme of an unmarried woman having a child and thereby promoting the idea of single motherhood and the decay of family values, a hot issue during that year's election campaigning. The producers and writers retaliated in the 60-minute season premiere which aired 21 September 1992. The clip from the debate was featured prominently in the episode (entitled "You Say Potatoe, I Say Potato") and the majority of the writing made fun of VP Quayle's remarks (To his credit, Vice President Quayle later sent the fictional baby Avery a very real plush toy elephant.)

The character Jim Dial was reportedly modeled after TV news reporter Jim Jensen of New York City's WCBS-TV.

Candice Bergen and the set of Murphy Brown made a guest appearance on Seinfeld (1989), in episode 3.23, Seinfeld: The Keys (1992) (where Kramer (Michael Richards) is hired, as an actor, to play Murphy's secretary), Jerry Seinfeld and Larry David returned the favour by appearing as themselves on "Murphy Brown" creator Diane English's other sitcom, Love & War (1992), where they receive a Seinfeld script in which Kramer sleeps with Elaine (Julia Louis-Dreyfus). This also echoes Elaine's writing a "Murphy Brown" script in that episode.

Murphy Brown (1988) became the longest running American primetime series then on the air when Married with Children (1986) ended on June 9, 1997 and retained that status until its final episode on May 18, 1998. It was succeeded by Family Matters (1989).

According to an article which ran in Ladies Home Journal in March 2000, CBS initially wanted Heather Locklear to play the title role.

Enjoyed a 3 year 1989-92 ratings high when it aired back-to-back with other CBS hit show Designing Women (1986)

This is the third time Jake McDorman (Avery Brown) and Anneleigh Tipton appear as a couple in a TV show.

The first 10 seasons of Murphy Brown were filmed in Burbank, CA. Starting with the reboot in Season 11, the show is filmed at Kaufman-Astoria Studios in Queens, NY.

Diane English: the series creator appeared on the last episode as a doctor.