A few decades in the future, a mercenary named Toorop (Vin Diesel) accepts a contract from a Russian mobster, Gorsky, who instructs him to bring a young woman only known as Aurora (Mélanie Thierry) to New York. In order to reach his goal, Gorsky gave Toorop a variety of weapons as well as a UN passport that has to be injected under the skin of the neck. Toorop, along with the girl and her guardian nun Sister Rebeka (Michelle Yeoh), travel from the Noelite Convent where they lived across Russia to reach America.

The towns and cities of Russia have been turned into dangerous, over populated slums by war and terrorist activity, forcing Toorop, Aurora, and Rebeka to face dangers of the human element, all the while fleeing from an unknown group of mercenaries claiming to have been sent by Aurora's supposedly dead father. The stress of humanity's situation causes Aurora to act out in strange ways that neither Toorop, nor Rebeka can explain. On one such occasion, Aurora seemed, for no reason, to panic and run from a crowded train station, just before it was bombed.

Later, they were forced to board a submarine that carried refugees to Canada. There were too many refugees to take at once, so the submarine was forced to leave some behind, even if it came to shooting them. Aurora, infuriated by the loss of life, suddenly knew how to operate the thirty year old submarine, without having ever learned about it.

Sister Rebeka explains to Toorop that Aurora could speak nineteen different languages by the age of two, and always seemed to know things she had never learned. When, three months before leaving with Toorop, she had begun acting out in ways she never had before. This occurred after a visit by a Noelite doctor who had administered a pill to Aurora. The doctor told her to go to America, and arranged for Toorop to take them.

Once in New York, a news broadcast about the bombing of the Convent that Aurora and Rebeka hail from, caused the group to realize that there was more going on than they knew. Gorsky, working for the Noelites, had planted a tracking device in Toorop's passport, and then bombed the convent when he knew they were in America. The doctor who earlier saw Aurora in the convent then appears to examine her again. When he leaves, Aurora reveals (again without being told) that she is pregnant with twins, even though she was a virgin.

Looking outside, Toorop saw both Gorsky's men, as well as the Noelite group, heavily armed and waiting for them. The High Priestess then calls Toorop and asks him to bring Aurora outside. Just before they take her away, Toorop changes his mind and starts a firefight with the two groups with the ultimate goal of getting the two women to safety. However, because of the tracking devices, Gorsky's men can lock onto him with tracking rockets. Rebeka gets shot and killed defending Aurora, who in turn shoots Toorop saying the words "I need you to live." By dying, the rocket goes off target and hits Aurora instead.

Toorop's body was revived by Dr. Arthur Darquandier, using advanced medical techniques that involved replacing his right arm and left leg with cybernetics to undo the damage of being dead for over two hours. Darquandier explaines that when Aurora was a fetus, he genetically enhanced her by using a super computer to 'implant' intelligence into her brain. It is also implied that the Noelite group had him create Aurora to become pregnant at a certain time in order to use her as a 'virgin birth' for their religion.

After she was born, the Noelites had him assassinated, or so they thought. He remained 'dead' until he found his daughter in Russia with Toorop.

Doctor Darquandier then instructed Toorop to find Aurora before the Noelites could, which he does. Aurora dies giving birth to two children of two different colors, whom Toorop raises as his own.

Mathieu Kassovitz developed an English-language film adaptation of Maurice Georges Dantec's French novel Babylon Babies for five years; in June 2005, this project got financed from StudioCanal and Twentieth Century Fox. The adapted screenplay was written by Kassovitz and screenwriter Éric Besnard. Production was initially slated to begin in February 2006 in Canada and Eastern Europe. French actor Vincent Cassel was initially sought to be cast in the lead role. In February 2006, actor Vin Diesel entered negotiations to star in the film, titled Babylon A.D., dropping out of the lead role of Hitman in the process. Production of the futuristic thriller about genetic manipulation was slated to begin in June 2006. By February 2007, filming was slated to wrap in April to release Babylon A.D. in time for the coming Thanksgiving. In February, filming took place at Barrandov Studios. In March 2007, the filming crew, having shot in the Czech Republic, took a two-week hiatus to deal with uncooperative weather, such as the lack of snow, and problems with set construction. Crew members scouted Iceland for locations with snow to shoot six to eight days of footage, which was supposed to be done in February. Filming was also done with the leads Diesel, Michelle Yeoh, and Mélanie Thierry in Ostrava in March. The French visual effects company BUF Compagnie was contracted to develop the film's effects.

In April 2007, Babylon A.D. was reported to be over-budget and three weeks behind schedule. A lack of snow meant a skiing sequence to be shot in Eastern Europe had to be moved to Sweden. Later in the month, actor Lambert Wilson was cast into the film. Filming was completed in May 2007.

American artist Khem Caigan designed the sigil that appears as a tattoo on the right side of Toorop's neck - an emblem which originally appeared in the Schlangekraft Necronomicon in 1977.

The music of Babylon A.D. is scored by composers Hans Zimmer and Atli Örvarsson. The musical alliance Achozen, represented by Shavo Odadjian and RZA performed the score for the film. Zimmer described the intended style: "Musically, our objective was to merge the sounds and energies of hip hop with classical music, seamlessly melting them into an unusual soundscape."