Nightow was born in Yokohama, and moved to
Yokosuka when he was in elementary school, and spent his junior high and high school years in
Shizuoka. His first exposure to comics was through
Tensai Bakabon, and he was also influenced by the comics of
Leiji Matsumoto such as Yamato, Harlock and 999. He also was drawn to the work done in Shonen Sunday which included artists
Rumiko Takahashi and
Fujihiko Hosono. Regarding "new wave" artists, he liked
Katsuhiro Otomo from Sayonara Nippon, and Fumiko Takano.
He studied social science and then majored in media studies at
Housei University. While there, he drew manga as a hobby, and made some
dojinshi. After graduation, he worked
Sekisui House where he sold apartments. After three and a half years, he quit his job to draw full-time. His first
one-shot manga was based on the popular
video game franchise
Samurai Spirits. He had also developed a story titled Call XXXX which was published in Super Jump magazine.
With the help of a publisher friend, he submitted a Trigun story for the February 1995 issue of the
Tokuma Shoten magazine Shōnen Captain, and began regular
serialization two months later in April. However, Shōnen Captain was canceled early in 1997, and when Nightow was approached by the magazine
Young King Ours, published by
Shōnen Gahōsha, they were interested in him beginning a new work. Nightow though, was troubled by the idea of leaving Trigun incomplete, and requested to be allowed to finish the series.
 The publishers were sympathetic, and the manga resumed in 1998 as Trigun Maximum (トライガンマキシマム Toraigan Makishimamu). The story jumps forward two years with the start of Maximum. Despite this, Nightow has stated
 that the new title was purely down to the change of publishers.
 Trigun Maximum ran until 2007 and generated 14 tankōbon volumes. The Trigun series was adapted into an anime series by
Madhouse and had a limited broadcast run in 1998. It received an English adaptation which aired on Cartoon Network. Its popularity in the United States resulted in creation of a feature film
Trigun: Badlands Rumble in 2010.
Nightow created the characters and story for the
third-person shooter video game series
 The series also received an anime adaptation.
In 2009, Nightow started a new manga series
Blood Blockade Battlefront, which was serialized in
Jump Square various magazines from Jump Sq.19 to Jump Sq. Crown. The series follows the adventures of a photographer who acquires supernatural visions and gets involved in an organization to fight monsters and terrorists.