A century and a half later, Mephistopheles reaches out to 17-year-old stunt motorcycle rider Johnny Blaze (Matt Long), offering to cure his father's lung cancer in exchange for Blaze's soul. The next morning, Blaze awakes to discover that his father's cancer is cured, but his father is killed that same day in a motorcycle stunt in which he falls into the ring of fire he is jumping through. Blaze accuses Mephistopheles of causing his father's death, but Mephistopheles considers their contract to be fulfilled.
Years later, Blaze (Nicolas Cage) has become a famous stunt rider. Blaze meets his former childhood sweetheart Roxanne Simpson (Eva Mendes), now a journalist, who he abandoned after his father's death. He convinces her he wishes to make amends and she agrees to a dinner date. Meanwhile, Blackheart (Wes Bentley), the demonic son of Mephistopheles, comes to Earth, along with three fallen angels. They are tasked to find the lost contract of San Venganza. In response, Mephistopheles makes Blaze the new Ghost Rider, and offers him his soul back in return for defeating Blackheart. Blaze is driven straight to the station on his "first ride", where he transforms into the Ghost Rider and a fight with the fallen angels ensues. The next day, he meets a man called the Caretaker (Sam Elliott), who seems to know all about the history of the Ghost Rider. He tells him everything that happened wasn't a dream and that it will happen again, especially when he is near evil.
When he arrives home, Blaze finds Simpson and reveals himself as the Devil's bounty hunter. Unconvinced, she leaves in anger and disbelief. After a brief imprisonment for the murders Blackheart committed, Blaze goes to the Caretaker for advice. The Caretaker tells him of his predecessor, Carter Slade, a Texas Ranger who hid the contract of San Venganza. Blaze returns home to find that Blackheart has killed his friend Mack (Donal Logue) and already has taken Simpson captive, threatening to kill her if Blaze does not deliver the contract to him.
Blaze returns to the Caretaker and obtains the contract. The Caretaker reveals that he is Carter Slade. Slade tells Blaze that he is more powerful than his predecessors, since he sold his soul for love as opposed to greed. The two leave for San Venganza. Slade gives Blaze his lever action shotgun before fading away.
After killing one of the fallen angels, Blaze gives the contract to Blackheart. He quickly transforms into Ghost Rider in an effort to subdue Blackheart, but dawn comes and he is rendered powerless. Blackheart uses the contract to absorb the thousand souls into his body. He attempts to kill Blaze, but is distracted when Simpson uses Blaze's discarded shotgun to separate them. After Blaze tries to kill Blackheart with the shotgun, he moves in and uses his Penance Stare to render him catatonic, burning all the corrupt souls within Blackheart.
Mephistopheles appears and gives Blaze his soul, offering to take back the curse of the Ghost Rider. Blaze refuses, saying that he will use his power against him, and against all harm that comes to the innocent. Infuriated of being robbed of the power, Mephistopheles vows to make Blaze pay, but Blaze tells Mephistopheles that he is not afraid. Mephistopheles then disappears, taking Blackheart's body with him. Later, Simpson tells Blaze that he got his second chance before sharing a final kiss with him. Blaze then rides away on his motorcycle, turning into the Ghost Rider.