In 1898, Sir Robert Beaumont, the primary financier of a railroad project in Tsavo, Kenya, is furious because the project is running behind schedule. He seeks out the expertise of John Henry Patterson, an Irish military engineer, to get the project back on track. Patterson travels from England to Tsavo, telling his wife, Helena, he will complete the project and be back in London for the birth of their son. He meets supervisors Angus Starling and Samuel (the film's narrator), and the doctor, David Hawthorne. Hawthorne tells Patterson of a recent lion attack.
That night, Patterson kills an approaching lion with one shot, earning the respect of the workmen. The project gets back on schedule. However, not long afterwards Mahina, the construction foreman, is dragged from his tent in the middle of the night. His half-eaten body is found the next morning. Patterson then attempts a second night-time lion hunt, but the following morning another worker is found dead at the opposite end of the camp from Patterson's position.
Patterson's only comfort now is the letters he receives from his wife. Soon, while the workers are gathering wood and building firepits around the tents, a lion attacks the camp in the middle of the day. While Patterson, Starling and Samuel are tracking it to one end of the camp, another lion leaps upon them from the roof of a building, killing Starling with a slash to the throat and injuring Patterson. Despite the latter's efforts to kill them, both lions escape.
Samuel states that there has never been a pair of man-eaters; they have always been solitary hunters. The men, led by Abdullah, begin to turn on Patterson. They dub the lions "the Ghost" and "the Darkness" because of their notorious methods of attack, and work on the bridge comes to a halt. Patterson requests soldiers from England to protect the workers, but is denied. During a visit to the camp, Beaumont tells Patterson he will ruin his reputation if the bridge is not finished on time and that he will contact the famous hunter Charles Remington to help because Patterson has been unable to kill the animals.
When Remington arrives with skilled Maasai warriors to help kill the lions, the initial attempt fails when Patterson's borrowed gun misfires. The warriors decide to leave, but Remington stays behind. He constructs a new hospital for sick and injured workers and tempts the lions to the abandoned building with animal parts and blood.
When the lions fall for the trap, Remington and Patterson shoot at them; they flee and attack the new hospital, killing many patients and Dr. Hawthorne. Abdullah and the construction men leave, and only Patterson, Remington, and Samuel remain behind to face the marauders. Patterson and Remington locate the animals' lair, discovering the bones of dozens of the lions' victims. That night, Remington kills one of the pair by using Patterson and a baboon as bait. The men celebrate, though later Patterson dreams about his wife and infant son visiting him in Tsavo, only for them to be killed by the remaining lion before he can get to them.
Waking from his nightmare the next morning, Patterson discovers that the remaining lion has dragged Remington from his tent and killed him; Patterson and Samuel cremate Remington's corpse on a pyre at the spot where he died. Grief-stricken and desperate to end the carnage, the two men burn the tall grass surrounding the camp, driving the surviving lion toward the camp (and the ambush they set there).
The lion attacks Patterson and Samuel on the partially constructed bridge and after a lengthy fight, Patterson finally kills it. Abdullah and the construction men return, and the bridge is completed on time. The film ends with Patterson's wife arriving with their son, and a narration by Samuel, who informs the audience that the lions are now on display at the Field Museum in Chicago, Illinois. Even today, he says, "if you dare lock eyes with them, you will be afraid".
- Jim Cummings as Winnie the Pooh/Tigger
- Travis Oates as Piglet
- Tom Kenny as Rabbit
- Bud Luckey as Eeyore
- Veronica Taylor as Ash Ketchum
- Ikue Otani as Pikachu
- Rachael Lillis as Misty
- Satomi Korogi as Togepi
- Eric Stuart as Brock
- Rob Lowe as Simba
- Gabrielle Union as Nala
- Kevin Schon as Timon
- Ernie Sabella as Pumbaa
- Bert Iwan as Mickey Mouse
- Tony Anselmo as Donald Duck
- Bill Farmer as Goofy
- Joel McCrary as Baloo
- Val Kilmer as Col. John Henry Patterson
- Michael Douglas as Charles Remington
- John Kani as Samuel
- Brian McCardie as Angus Starling
- Bernard Hill as Doctor David Hawthorne
- Tom Wilkinson as Sir Robert Beaumont
- Emily Mortimer as Helena Patterson
- Om Puri as Abdullah
- Henry Cele as Mahina
- Ash Ketchum, Pikachu, Misty, Togepi, Brock, Simba, Nala, Timon, Pumbaa, Mickey Mouse, Donald Duck, Goofy, and Baloo will guest star in this movie.
- This film will be dedicated to Jerry Goldsmith (1929-2004), who composed the music for the real film and died from colon cancer, Vilmos Zsigmond (1930-2016), who did the cinematography for the real film and died from an unknown cause, and Henry Cele (1949-2007), who played Mahina and died from an infection.