Plot hole: The apartment block where Will lives supposedly has the same layout for each floor of the building. Yet in "Yours, Mine or Ours" the room 12D is seen as located right in front of the elevator, the same location as Will's apartment door - however Will's apartment is always seen as 9C.
Plot hole: In the episode "Lows in The Mid-Eighties" during the flashback scenes, it is shown to us that Will comes out of the closet during his freshmen year of college during Thanksgiving Break, when they spend the weekend at Grace's Parents house. However in the episode "Willian, tell" Grace claims that Will came out to her at senior year of college during Christmas Break. Quite a difference for such a memorable time.
Plot hole: In "Alley Cats" when they are bowling and Grace is losing, she says she's fine with it and she knows how it feels to be her middle sister, then Will reminds her that she's actually, "The baby of the family looking for Daddy's approval." However, in all later episodes, Grace is portrayed as the miidle child with a younger sister, Joyce and an older one called Janice. This mistake is made in a few other places through the show, where Grace either refers to how old she is (youngest, middle child etc) incorrectly.
Continuity mistake: In the episode "Grace, Replaced", with the neighbor Val who moves into "apartment 15F" in the same building as Will and Grace. Yet in the previous episode "Yours, Mine or Ours" with Peter (who moved into 12D) we learn that 12 is the highest floor in the building...