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Born in New York City on June 23, 1964 as Joseph1 Hill Whedon, and being a third-generation TV writer, he is a son of Tom Whedon, a screenwriter for Alice in the 1970s and The Golden Girls in the 1980s, and a grandson of John Whedon, who worked on The Donna Reed Show in the 1950s and The Dick Van Dyke Show in the 1960s. His mother, Ann Lee (nee Jeffries) Stearns, originally from Kentucky, was a teacher at Riverdale Country School as Lee Whedon, and an aspiring novelist. His parents had both acted, and appeared in a play together at the Harvard Radcliffe Dramatic Club. Whedon is the younger sibling of Samuel and Matthew Whedon and older sibling of writers Jed and Zack Whedon.

In 1997, Whedon created his first television series, Buffy the Vampire Slayer.2 The series depicts Buffy Summers, the latest in a line of young women called to battle against vampires, demons, and other forces of darkness. The idea came directly from his aversion to seeing the Hollywood formula of "the little blonde girl who goes into a dark alley and gets killed in every horror movie". Whedon said he wanted to subvert the idea and create someone who was a hero. This conception came from "the very first mission statement of the show, which was the joy of female power: having it, using it, sharing it". The writing process came together from conversations about the emotional issues facing Buffy Summers, and how she would confront them in her battle against supernatural forces. Whedon usually directed episodes from his own scripts that held the most cathartic moments in Buffy's story.  The series received numerous awards and nominations, including an Emmy Award nomination for the 1999 episode "Hush". The 2001 episode "The Body" was nominated for a Nebula Award in 2002, and the fall 2001 musical episode "Once More, with Feeling" was nominated for a Best Dramatic Presentation Hugo Award and a Best Script Nebula Award. The final episode "Chosen" was nominated for a Best Dramatic Presentation, Short Form Hugo Award in 2003. All written and directed by Whedon, they are considered some the most effective and popular episodes of the series.  Scholar A. Asbjorn Jon recognized that the series has shifted the way vampires have since been depicted in popular culture representations. Since the end of the series, Whedon has stated that his initial intention was to produce a "cult" television series and acknowledged a corresponding "rabid, almost insane fan base" that subsequently emerged. In June 2012, Slate magazine identified it as the most written about popular culture text of all time. "[M]ore than twice as many papers, essays, and books have been devoted to the vampire drama than any of our other choices--so many that we stopped counting when we hit 200".  A lifelong comic book fan, Whedon authored the Dark Horse Comics miniseries Fray, which takes place in the far future of the Buffyverse. Like many writers of the show, he contributed to the series' comic book continuation, writing for the anthology Tales of the Slayers, and the main storyline of the miniseries Tales of the Vampires. Whedon and the other writers then released a new ongoing series, taking place after the series finale "Chosen", which he officially recognizes as the canonical eighth season. Whedon returned to the world of Fray during the season eight-story arc "Time of Your Life". Buffy the Vampire Slayer Season Nine was published from August 2011 to September 2013, for which Whedon wrote "Freefall, Part I-II" (with Andrew Chambliss).
Joss Whedon