(Capcom's primary storyline)
Early life and Terragrigia Panic
At a young age, Natalia lived with her parents in Terragrigia. When she was 3, Natalia lost her parents in during the Terragrigia Panic, a terrorist attack on the city by Il Veltro. Here she was rescued by TerraSave chief Neil Fisher, who took her off Terragrigia before its destruction and gave her a teddy bear she named Lottie. From then on, she grew under the care of TerraSave. Due to these traumatic events, Natalia suffered an enormous blow to her psyche, leaving her with a limited emotional range and a seemingly inability to feel fear.
During an assault on TerraSave's HQ, Natalia was abducted along many TerraSave members and was sent to an uncharted island where she was injected with the T-Phobos Virus and equipped with a bracelet that monitored fear and mutations.
Natalia later reached an abandoned city, where she once again saw Claire and Moira, but was stopped by them before running away. They introduced themselves and traveled together for a small while, with Natalia helping them pass a locked door by crawling though a hole in the wall.
A short time after that, a helicopter piloted by Gabriel Chavez, flew near them with hope of using it to take them all off the island. However, the Overseer caused the helicopter to crash remotely. While Moira and Natalia were distracted, Neil Fisher, who was working with the Overseer, captured Natalia and took her to the Overseer's central facility.
Later after talking for a short while with the Overseer, revealed to have been Alex Wesker, Natalia was made to sleep in a stasis pod, where Alex transferred a digitized copy of her consciousness into Natalia's brain and sent her to sleep beneath the facility for 6 months while the consciousness transfer finalized.
Six Months Later
Natalia awoke 6 months later from her stasis pod. She can't remember anything about what had happened to her on the island, and begins to wonder why she was there. Natalia encounters another Natalia, who claims to have a letter from Lottie. They then travel across the island compound looking for Lottie, with Dark Natalia making snide comments along the way. Natalia finally discovers Lottie, only to realize that it was all a trap devised by Alex Wesker's half of consciousness inside her. Dark Natalia and Lottie disappear, leaving Natalia finding herself standing in front of the port, where she meets Barry for the first time.
Barry interacts with her when he arrives at the island looking for his abducted daughter Moira. When questioned about why she is on the island, she explains that she doesn't have any parents and she doesn't know why she is on the island. Though he initially wants Natalia to stay at the boat, Barry allows Natalia to accompany him through the island in order to protect her. He soon discovers that Natalia does not fear the enemies and that she possesses the ability to sense their presence.
They work together and eventually reaches the radio tower after braving the horrors of the prison and the forest outside of it. Barry learns that six months had passed since Moira had sent her transmission. Upon hearing her name, Natalia experiences a headache and explains her experience about Claire and Moira. Natalia reveals that Moira had died, much to Barry's shock. Natalia leads Barry to a ruined tower in the island's abandoned city, where Moira went six months ago with Claire.
They venture further into the island's compounds, encountering mutated Pedro Fernandez, a Terra Save member who Claire fought earlier, and a burned corpse of Gabriel Chavez. They eventually reach the tower's remains, where they find a painting depicting Albert Wesker and a blonde woman in a white coat. Natalia, scared by her painting, reveals that she is Alex Wesker. Barry was angrily dismayed after hearing of two Weskers. A laughter is heard from a feminine creature, who disarms Barry and points her finger at Natalia.
The cloaked figure reveals itself as Alex Wesker, the island's Overseer, living in a monstrous state. Alex gloats about having killed and buried Moira alongside the inhabitants of Sushestvovanie Island, and proceeds by summoning a group of Revenant. Barely surviving the encounter, destroying the chamber they were in by shooting the room's fragile construction, Barry chooses to protect Natalia at all cost. The two work their way to escape the island's mines and out to the abandoned village.
Unknown to them, Alex stalked them along the way. She incapacitated Barry by throwing him off a cliff, thus making Natalia defenseless. With no more barrier between them, Alex expresses her rage on Natalia, questioning why Natalia didn't mutate while she did, choking Natalia in the process. As Alex glares into Natalia's eyes, she begins to cower in terror and fled the scene.
The End of Nightmare
After reuniting with Barry, Natalia once again helped him to track down Alex, searching their way through the mines filled with noxious gas. Natalia receives threatening messages from Alex through her bracelets, intended to discourage her from pressing on. Much deeper in the mines, as the two are getting closer to Alex's hiding place, Natalia finds her teddy bear Lottie had been tore apart and nailed on a wall, much to her shock. They found and cornered Alex in her laboratory, only to realize Alex had injected herself with Uroboros virus to mutate and engage Barry in a grueling battle. After taking much injury, Alex then plays dead, attempting to do a surprise attack on Barry, which she did successfully to recapture Natalia.
Just before anything else can be done, Moira, using a handgun, saves Natalia and her father from the Monster Alex. The three of them have only a brief moment of relieve, as Monster Alex uses her tentacles to regenerate her body. Chasing them to the seaside cliffs, Natalia and the Burtons are cornered until Claire Redfield arrives to the rescue, wielding her sniper rifle. Taking Natalia and Moira to the helicopter, Barry and Claire battle together the monstrosity, which perished after taking huge damage and being shot by a RPG-7.
Safe at last, the four of them left in the helicopter as the BSAA arrived to clean up the island.
Later life (2013)
"A Cage went in search of a bird. But now the bird is gone. The bird has changed"
By 2013, Natalia was adopted by Barry and Kathy Burton and lived with them and her new sisters and was seen reading a book ("The Zürau Aphorisms"), surrounded by articles with headlines on Bioterrorism. Natalia mentions a line from the book, grinning maliciously, suggesting that Alex's copied consciousness lives on in Natalia's body.
If during Claire's part of Episode 3: Judgment, Moira does not finish off Neil Fisher, a non-canonical ending occurs in Episode 4: Metamorphosis, when Natalia is grabbed by Alex, she will not be saved by Moira (since Moira did not conquer her fear of guns). Instead Alex's copied consciousness takes over and uses her suddenly enhanced strength to destroy the original Alex. She then proceeds to taunt a distraught Barry.