The film stars Keanu Reeves as John Constantine, a cynical exorcist with the ability to perceive and communicate with half-angels and half-demons in their true forms and to travel between Earth and Hell.

Rachel Weisz, Shia LaBeouf, Tilda Swinton, Pruitt Taylor Vince, Djimon Hounsou, Gavin Rossdale, and Peter Stormare also feature.

There, cynical occult expert John Constantine exorcises a demon from a young girl after witnessing its attempt to reach Earth through her, something that should be impossible because of the treaty between Heaven and Hell.

Suffering from terminal lung cancer, Constantine meets with the half-breed angel Gabriel to request an extension to his life in exchange for his work deporting Hell's forces.

At the morgue, Constantine's friend Father Hennessy discovers a mysterious symbol on Isabel's wrist but is killed by the half-breed demon Balthazar.

Constantine interrogates Balthazar, who reveals that the blood of Christ on the spear tip is Mammon's divine assistance, and Angela will be his host.

Resentful at God's favoritism for humanity and forgiveness for even the most wicked, Gabriel intends to unleash Hell on Earth so that those who survive will become truly worthy of His love.

Additionally, Michelle Monaghan filmed several scenes as Ellie, a half-breed demon Constantine sleeps with and asks for information, who is based on a succubus of the same name in the Hellblazer comics.

Constantine incorporated some elements of Garth Ennis's "Dangerous Habits" story arc from the comic (issues #41–46),[20] and others, such as the inclusion of Papa Midnite, from the Original Sins trade paperback.

[22] Reeves played the role of John Constantine with his real-life American accent and black hair,[22] while the character in the comics was drawn to resemble the blond musician Sting and came from Liverpool.

[23] For the film, Constantine was also given the psychic ability to see "half-breeds" as they truly are, and this led him to attempt suicide, causing his damnation,[24] which, in the comics, was punishment for summoning a demon that killed a young girl.

[25] Additionally, the resolution of the lung cancer plotline in the film was amended so that Lucifer willingly saves the redeemed Constantine to give him a second chance at falling, rather than being tricked into doing so.

[26] He further explained: That was actually a combination of me and the visual effects supervisor and the production designer sitting down and sort of coming up with the biological growth that's growing all over the cars and what that looks like and the color palette.

[38] He cited Keanu Reeves' ability to "retain his charisma in a weird-silly moment" as proof that he is a "movie star", and referred to Tilda Swinton as "immaculately decadent".

Ella Taylor of LA Weekly wrote: "Constantine, which opts in the end for what I can only describe as a kind of supernatural humanism, is not without its spiritual satisfactions".

[39] Carina Chocano of the Los Angeles Times said that "Keanu Reeves has no peer when it comes to playing these sort of messianic roles—he infuses them with a Zen blankness and serenity that somehow gets him through even the unlikeliest scenes with a quiet, unassuming dignity".

[42] Michael Sragow of The Baltimore Sun also gave the film 2 stars out of 4: "It all comes off as a case of filmmakers wanting to have their communion wafer and eat it, too".

He was not particularly critical of the acting, only mentioning it by stating: "Reeves has a deliberately morose energy level in the movie, as befits one who has seen Hell, walks among half-demons, and is dying.

[49] In 2011, director Francis Lawrence stated, regarding a sequel: It's interesting that over the years, Constantine seems like it's become ... like it has this sort of cult following, which has been great.

[50]In November 2012, Guillermo del Toro signed a deal to write and direct a Justice League Dark film centered around DC Comics' supernatural characters, John Constantine among them.

[52][53] In November 2020, Stormare announced in a post on Instagram that a sequel was "in the works", though neither representatives for Warner Bros. nor Reeves immediately responded to requests for comment.

[54] In September 2022, Deadline Hollywood reported that Warner Bros. would develop a Constantine sequel, with Keanu Reeves set to return in the lead role.

[55] Lawrence gave an update on the project in October 2023, indicating that work had proceeded following the conclusion of the 2023 Writers Guild of America strike; he, Reeves and Goldsman have been meeting and discussing the story.