First Kill is based on a short story of the same name written by Victoria Schwab, who also created the series.

Netflix ordered the series on October 15, 2020, consisting of eight one-hour episodes, and it was the first production from Emma Roberts and Karah Preiss's company Belletrist Productions.

Sarah Catherine Hook and Imani Lewis were cast in the lead roles on March 10, 2021, followed by the rest of the main cast including Elizabeth Mitchell and Aubin Wise on May 27, 2021.

Filming was scheduled to begin in late 2021 in Savannah, Georgia.

Jet Wilkinson was announced on April 21, 2021 to direct the first two episodes of the series.

In its first three days on Netflix, the show accumulated 30.34 million viewing hours globally, later surpassing 100 million hours after a month and peaking at number 3 on Netflix's Top 10 English-language TV list.

Despite decent viewership, Netflix canceled First Kill on August 2, 2022 after just one season, prompting a sustained fan campaign to get it renewed or picked up by another streaming service.

Critics and outlets noted the show's significance as a queer, Black-representation coming-of-age story, with Essence comparing it to a mash-up of Romeo and Juliet and The Vampire Diaries.