It revolves around a young photographer named Leonardo Watch, who obtains 'the All Seeing Eyes of the Gods' at the cost of his sister's eyesight.

After the incident, Leonardo moves to the city of Hellsalem's Lot to join an organization known as Libra to fight several monsters as well as terrorists.

Blood Blockade Battlefront was later serialized in Jump SQ.19 from May 2010 to February 2015, when the magazine ceased publication; Shueisha collected its chapters in ten tankōbon volumes.

A direct sequel, titled Blood Blockade Battlefront: Back 2 Back was serialized in Jump SQ.Crown from July 2015 to January 2018, when the magazine ceased publication, and the series was transferred to Jump SQ.Rise, where it ran from April 2018 to April 2022; its chapters were collected in ten tankōbon volumes.

A third series, titled Blood Blockade Battlefront: Beat 3 Peat started in Jump SQ.Rise in October 2022.

Blood Blockade Battlefront centers around the crime fighting organization "Libra" and their battles in Hellsalem's Lot, formerly known as New York City.

Hellsalem's Lot was created when a portal to the "Beyond" opened, becoming a paranormal melting pot of monsters, magic and the everyday mundane life, and it is up to Libra to clear the streets of trouble and prevent the horrors of this city from spreading to the outside world.

[5][6] It only featured very few members of the final cast and had a much different tone, with more emphasis on it being a vampire hunting story in a contemporary city.

A three-chapter series, titled Kekkai Sensen − Mafūgai Kessha (血界戦線 -魔封街結社-), was serialized in Jump Square from January 5 to March 4, 2009.

[16] On January 28, 2025, Dark Horse Comics announced that it will publish the series in a 3-in-1 omnibus edition, with the first volume set to be released on July 15 of the same year.

[25] A third series, titled Blood Blockade Battlefront: Beat 3 Peat, started in Jump SQ.Rise on October 26, 2022.

[50] For Blood Blockade Battlefront & Beyond, Unison Square Garden performed the opening theme "Fake Town Baby [ja]",[51] while Daoko and Yasuyuki Okamura (credited as Daoko × Yasuyuki Okamura) performed the ending theme "Step Up Love [ja]" (ステップアップ LOVE, Suteppu Appu Rabu).

Brigid Alverson from MTV Geek criticized the artwork for being hard to follow and stated "it boils down to a matter of taste.

Jacob Hope Chapman from Anime News Network praised the cast and studio Bones' work.

[59] Additionally, he liked the consistency in quality and commented "The contiguous threads laced through these episodic adventures are beginning to converge fast, and while I can't see the full picture yet, I know Rie Matsumoto is building the anime-original material of Leo's romance into something special.