- Jaimee Foxworth originally played the role of the youngest Winslow child, Judy. The combination of her character having little to do and Foxworth's request for a salary increase led producers to simply write her off the series. Later episodes revised the show's history so that Judy never existed and the only two Winslow children were Eddie and Laura.
- The character of Steve Urkel was named after a friend of one of the producers, and was only supposed to appear once. However, the audience's response was so overwhelmingly positive that the producers decided to make Urkel a regular character.
- The original ABC broadcasts, as well as the later airings on ABC Family, for episodes from the first three seasons use an extended version of the "As Days Go By" theme accompanied by clips from selected episodes. Syndication edits of "Family Matters" feature the abbreviated version of the theme used in season 4 through 6. On the ABC Family airings, there is an extended opening sequence, which presumably has not been used since the series originally aired on ABC.
- The theme song for the first five episodes was "What a Wonderful World" by Louis Armstrong. The series' more familiar theme, "As Days Go By", was first used in episode six.
- Many sets used in scenes inside the house were also used in _"Hogan Family, The" (1986)_ and _"Step By Step" (1991)_.
- JoMarie Payton's Harriet Winslow originated in Perfect Strangers as an elevator operator. Reginald VelJohnson also appeared as Carl on the show.
- The character of Steve Urkel was so popular, that it spawned a series of merchandise including a talking doll, trading cards, posters, books, lunchboxes and t-shirts. The character even had its own limited edition cereal.
- When ABC delayed making a decision to renew the show for a ninth season, CBS made a deal with Warner Bros. Television to renew the show for a ninth season, which would be its last.
- The show's producers hoped for a 10th and final season on CBS, but the ratings for the 1997-98 9th season were so bad that the network ended up canceling the show and airing the series finale with no fanfare during the summer season. In a nod to the stillborn plans to have Steve and Laura get married in a 10th season, the series finale did have them getting engaged.
- JoMarie Payton decided to leave the show when it moved networks from ABC to CBS because she didn't like how the show overemphasized the Steve Urkel character. Payton agreed to appear during the first half of the ninth season, after which she was replaced as Harriette Winslow by Judyann Elder.
- Jaleel White played eight characters total during the series. Of course, his original character is Steven Quincy Urkel. He also played his female cousin Myrtle Urkel in a few episodes and male cousin Cornelius Eugene Urkel (or "OGD: Original Gangsta Dawg") in one episode. He also provided the voice of his invention Urkel-Bot in two episodes. The remaining are Steve's alter-egos (in order of reverse length of appearance)... Stefan Urquelle, Bruce Lee, Elvis Presley, and Albert Einstein.
- Carl's middle name is Otis.
- Clyde Kusatsu plays Principal Edgar Shimada in three episodes (Fight the Good Fight, Woman of the People, and Presumed Urkel).
- Reginald VelJohnson is the only cast member to appear in all 215 episodes of the series.
- Laura's middle name is Lee.
- Carl, Estelle Eddie, Richie and 3J are the only five characters to use Steve's transformation chamber. Laura, and Harriet are the only two characters to not use it. Carl is the only character to use it more than once. Eddie used it off-screen.
- This show lasted one year longer than its parent series Perfect Strangers.
- Carl, Eddie, and Laura are the only three characters to transform into a nerd. Carl and Eddie used Steve's transformation chamber and Laura become a nerd due to a Christmas wish.
- The three inventions used on the show that actually worked (in order of episodes) were: the transformation chamber, the cloning machine, and the UrkPad.
- Some of the names for Steve's transformation chamber liquids are: Einstein Elixir, Bruce Juice, etc.
- This is the second longest running U.S sitcom with a predominately African-American cast. The Jeffersons surpasses it by one year.
- The Season 9 episode "Deck The Malls" is the last time Rachel, Richie, and Mother Winslow appear on the show. It was also the final episode for JoMarie Payton as Harriette.
- Every season contained an episode where a set is completely demolished.
- Jaleel White has played Steve Urkel on three ABC shows: Family Matters, Full House, and Step by Step.
- JoMarie Payton has played Harriette on two ABC shows: Perfect Strangers and Family Matters.
- Jaleel White and Telma Hopkins are the only two cast members to be credited with an "As" credit throughout the shows nine season run.
- Rosetta LeNoire was 85 years old by the time she left the show.
- JoMarie Payton was credited under three different names throughout the shows nine season run: JoMarie Payton-France, JoMarie Payton, and JoMarie Payton-Noble.
- Even though Carl is older than Harriette on the show, JoMarie Payton who plays Harriette is two years older than Reginald VelJohnson who plays Carl.
- Even though he plays the older brother, Darius McCrary is actually two months younger than Kellie Shanygne Williams who plays Laura, the middle child.
