Claire is the younger sister to Chris Redfield, and shares many of the same qualities of her older brother; in fact she can be quite the tomboy. For some time before the Raccoon City outbreak, Claire had not heard from her brother. Concerned for his welfare, she got on her bike and headed for Raccoon City, not knowing the nightmare that awaited her.

She discoverd the whole city had become a land of the undead. Claire then met up with rookie cop Leon Kennedy, and the two of them traveled to the R.P.D. where Claire hoped to find her brother. The two of them were separated after a car accident, but she still found her way into the police station. Claire found the S.T.A.R.S. office and discovered, from reading his journal, that Chris had left Raccoon City days earlier.

Claire pushed on, trying to find a way out of the police station. During her search she found a young girl named Sherry. Surprised that such a small girl could survive so long, she took Sherry with her. Together, they suffered through several hardships and horrors, including being chased by the mutated William Birkin. Sherry was infected with the G-virus by her father and Claire would stop at nothing to find a cure, who searched for and eventually found a vaccine in the underground Umbrella lab. She administered the vaccine to Sherry and the two of them escaped, along with Leon, on a train out of Raccoon City. After a brief encounter with the G-virus infected Birkin, the whole group was finally free.

In the following months Claire made it her mission to find her brother Chris. Fearing that Umbrella might have captured him, she headed for Umbrella headquarters. She was captured while snooping around the Umbrella headquarters and sent to an island that housed one of Umbrella's prisons for Umbrella.

While imprisoned on the island, it was assaulted and Claire was let out of her cell only to find the island was now crawling with zombies. Claire found a computer and contacted Leon, informing him of her situation hoping that Chris would get in contect with him. On the island, Claire also met up with a young man named Steve, a former prisoner at the base, as well. The two of them made their way around the island while trying to avoid the traps set by the owner Alfred Ashford, managing to escape the island on a plane that was programmed to fly automatically to a base in Antartica.

While in Antartica Claire and Steve began to get really close, and Claire realized she had feelings for the sometimes annoying Steve. Their story would not have a happy ending, however, as Steve was captured by Alexia and infected with the T-Veronica virus. Claire was captured as well, but Chris managed to find and free her. Claire told Chris that she had to find Steve and went in search of him. Claire found Steve trapped in a large cell, but the virus had alreday transformed him into a huge beast. Claire ran for her life as the creature that was once Steve pursued. At that moment, one of Alexia’s tentacles wrapped itself around Claire, trapping her. Steve, a huge battle-axe in hand, was about to kill her as well, but managed to stop himself. Instead, he struck the tentacle, freeing Claire, which in turn struck Steve. Steve returned to his normal self, now mortally wounded, and professed his love for Claire as he died in her arms.

Claire regained her composure and rejoined her brother as they searched for a way out of the base, eventually finding a jet that Chris could pilot. After a few delays, they finally managed to escape the base.

In the subsequent years, Umbrella was destroyed, but some major players such as Wesker remained.