The show, which has been widely credited with bringing gay television characters out of the closet, concluded with a tear-jerking finale that looked to the future.
The final episode was preceded by a montage of bloopers and sentimental reflections on the sitcom by its actors.
"I'm proud of being a part of something in history and I'm proud to have been given a platform to make people laugh," says Sean Hayes, who played Jack.
Eric McCormack (Will) adds: "We have never taken ourselves or this show too seriously but now that it's over I take our collective achievement very, very seriously."
Fans gathered at a club in West Hollywood for a Will & Grace finale viewing party.
"You could feel the energy in the room that everyone was just really excited to see what was going to happen," says Bryan Carney.
The final farewell features all the main characters growing old and slightly grey.
"My favourite moment was when you had them singing Unforgettable to each other. The look in Jack and Karen's eyes - it transcended the moment, you saw that this image could last in your mind forever," says Mr Carney.
"At the end it was a little sappy, but how else would you expect it to end? It's a show of eight years about friendship and love amongst a culture that has not had acceptance for such a long period of time."
The sitcom has picked up a string of Emmy awards and achieved more critical acclaim than any other comedy featuring openly gay lead characters.
From the start, the premise was a simple one. A gay man, Will, and his straight friend Grace (Debra Messing) share a flat together in New York. Will's platonic pal Jack is also gay - and flamboyant with it.
Together with Grace's assistant, Karen (Megan Mullally), who is outrageous in her own way, the four main characters lead their lives of ups and downs.
They struggle with relationships, test their friendships to the limit and poke fun at each others' sex lives.
"Will & Grace has brought tremendous visibility to the gay and lesbian community and has provided, not just our community, but all the viewers, an opportunity to laugh along with gay and lesbian characters, not just laugh at them," says Corri Planck, a gay rights activist and media relations consultant in Los Angeles.
"They were the butt of jokes but the jokes were from other gay people and that was a different kind of experience for a lot of viewers.
"For a comedy it took on some challenging issues and it did it with great humour - relationships and marriage and parenting."
At its peak, the show attracted a huge audience - regularly finding a place in the top ten list of most-watched shows.
The viewers were young and old alike - with many a 'soccer mom' or elderly granny rooting for Will to find a boyfriend.
Hayes hammed up his camp character's personality for laughs and won legions of loyal fans - gay and straight.
"What happened with Will & Grace is that American viewers had an opportunity to let these characters become part of their lives," says Ms Planck.
"It's a sitcom and its job is to be funny, and Will & Grace was exceptionally funny and did a great job."
Before Will & Grace there was Ellen. But comedienne star Ellen DeGeneres suffered a major career setback when her sitcom was cancelled in 1998, shortly after the revelation that her character was a lesbian.
DeGeneres, who is openly gay, now has a hugely successful talk show on daytime TV.
But the primetime schedules on the main networks still feature predominately heterosexual characters.
"A lot of gay and lesbian characters pop up in reality television programmes and cable has done an excellent job here in the United States in including gay and lesbian characters in their programming," says Ms Planck
"That's thanks in large part to programmes like Queer As Folk and The L Word but in broadcast television we still see a dramatic under-representation."