The panel's moderator also began by paying tribute to 53-year-old Gisela Gagliardi of New York, saying she "will always live in our hearts and memories."
But the sadness was quickly replaced by frenzied screams as Stewart, Pattinson, Lautner and fellow cast members Peter Facinelli, Ashley Greene, Nikki Reed, Elizabeth Reaser, Kellan Lutz and series author Stephenie Meyer took the stage.
Director Bill Condon appeared via video from London, where he is recording the score for the film.
"Everyone knows the phenomenon of 'Twilight' really exploded here [at Comic-Con], and we're all aware, too, this is the last time," he said. "Twilight" first inspired a Beatlemania-style response when the cast of the beloved best-seller was introduced at the annual pop-culture convention four years ago.
The opening moments of "Breaking Dawn Part 2" show Bella Swan (Stewart) adjusting to her new life as a vampire. It was fun for Stewart, too.
"It felt so good to break her in, to see how fast the car goes," she said from the stage after the footage was shown. " 'Twilight' vampires are very unique. They're not like all vampires. … Everyone's powers are informed by how they were when they were human. I love her. I think she's the coolest one, so I had fun doing it."
Reed said she feels like she came of age during the production of the "Twilight" films. "We were kids when we started this," the 24-year-old actress said. "We're growing into adults and we're all at different places in our lives."
Stewart said appearing with her "Twilight" castmates for their final Comic-Con panel "is kind of sad, man."
"This is sad right now, to be honest," she said. "We got to live here, we got to live in this world for such a crazy long period of time compared to the amount of time you usually do, but it feels good. It's like, 'Yes we did it. Yes, we finished.' "
Meyer has already moved on. She closed the panel by showing a clip from her latest adapted novel, the sci-fi thriller "The Host."
"The Twilight Saga: Breaking Dawn Part 2" opens Nov. 16. Comic-Con continues through Sunday.