Mithril, a covert military institution using state-of-the-art technology to combat terrorist operations, assigns a specialized team to a sensitive mission. Under the command of superior officer Melissa Mao, sergeants Sousuke Sagara and Kurz Weber must secretly protect Kaname Chidori—a teenage girl who unconsciously holds breakthrough scientific knowledge and is considered a "Whispered"—from intelligence agencies and other organizations pursuing her abilities.

While Kurz and Melissa are to assist him remotely, Sousuke enrolls at Kaname's high school as one of her classmates to closely monitor her. However, his militaristic upbringing and poor social skills lead to a difficult adjustment to civilian life. Not only does he attract unnecessary attention, but his actions frequently make Kaname suspicious of him.

Despite the earnest attempts to fulfill his duty, a terrorist ambush further complicates Sousuke's task. Recognizing the vicious mastermind behind the assault, Sousuke abandons his orders to ensure Kaname's safety.

Full Metal Panic! adapts the first three volumes of Shoji Gatoh's light novel series of the same title, as well as content from the first three volumes of the spin-off series Full Metal Panic! Tanpenshuu. Among the differences between the light novels and the anime series, the most notable are episodes 14 to 17, which are anime original stories.

The series was initially scheduled to air on WOWOW before 2002, but it was postponed on account of the September 11, 2001 World Trade Center attacks. ADV Films, the licensor for North America, released the anime on the Anime Network on demand between 2003 and 2004. Full Metal Panic! is Gonzo's first anime to receive a dubbed version in Tagalog language.

In Japan, the series was made available on 12 DVDs between February 25, 2002 and January 25, 2003. In North America, seven DVDs were released from June 10, 2003 to February 17, 2004. Additionally, two DVD box sets including the complete collection were also published: one on April 19, 2004 and the other on June 3, 2008.