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The characters were designed by Keiji Nakaoka while the soundtrack is by Norihiko Hibino'sGEM Impact studio.The animation was produced by Production I.G, and the game was released in 2009.

The player plays as a modern-day ninja, using a katana, twin swords and broad sword as the main weapon to the hostile creatures. Combat system is similar to Ninja Gaiden or Devil May Cry. A chi bar is used up when "ninja vision" or ninjutsu is used. The gameplay is highly cinematic, relying on quick time events to finish missions; after attacking a boss until the health bar is empty, the player must perform a finishing move, called the todome.

In 2011, a small village was attacked by unknown creatures and the survivors were moved to a research facility where they underwent examination. While at the research facility, the survivors began to show symptoms of necrotizing fasciitis it was found out they are infected by a strange type of hookworm parasite, which was classified as "Alpha-worm". Conventional medicine had no effects on the patients and the worms deformed the victims, but the infection increased the strength and resilience of the people infected. The infected eventually broke free and attacked the researchers and, due to a fear of an outbreak, the military assaulted the facility and destroyed all traces of the infected. To prevent panic, governments of the world kept the Alpha-worms secret. The G.U.I.D.E (Global United Infestation Detection and Elimination) force was formed by Agent Michael Wilson, recruiting elite operatives from around the world. Eventually, after a massive outbreak of Alpha-worm infestation takes over the city of Tokyo, an elite ninja team including the young Ken Ogawa, and led by his father Kanbe, is sent to deal with the situation.

The concept for Ninja Blade initially came when From Software thrived to create a game that conveyed to the gamer the same intense sequences from those of Hollywood action films. From Software worked with Microsoft in creating the game's protagonist, Ken Ogawa. Ninja Blade producer Masanori Takeuchi states: "We worked closely with Microsoft in creating Ken. They provided us with lots of useful feedback and insightful consumer research of worldwide gamers. By cooperating and working together, Ken has become more appealing to a wider audience." Character of Ken Ogawa was designed by Capcom 2nd Character Development Studio designer Keiji Nakaoka.

Ninja Blade was commonly referred to as Otogi 3 by various sources before its official announcement. Ninja Blade planner Kazuhiro Hamatani noted that while not a direct sequel or spiritual successor to Otogi, that the game would contain action-adventure elements of which fans of the Otogi series would like.

A demo for Ninja Blade was released in Japan on December 29, 2008. The demo was released in North America on March 10, 2009.

Overall, the game has received mixed to positive reviews, with an aggregate score of 68/100 on Metacritic.

Ninja Blade was named Game of the Month in the June 2009 issue of GamePro, with a rating of 5/5 stars.In GameSpot's The Best of 2009 awards, it was one of the five titles nominated for Best Game No One Played.

In 2011, UGO.com included the todome in their list of the nastiest cinematic kills in games.