Fred was born in Dallas, Texas to Roger and Patricia "Trish" Burkle. When she reached adulthood and graduated from high school, she moved to Los Angeles for college. Originally majoring in history, Fred took a physics class with Professor Seidel which inspired her to take another path. Around this time, she began working at Stewart Brunell Public Library. In 1996, while shelving a demon language book, a curious Fred recited the cryptic text out loud and was accidentally sucked into a dimensional portal to Pylea. It was later discovered that the portal was actually opened by Fred's jealous college professor, Professor Seidel, who had sent every promising student to it, essentially sending them to their death; Fred was the only one of at least six to return (cf. "Supersymmetry"). In high school or college, Fred was a marijuana user as shown in the Episode, Spin The Bottle. In that episode she asks Wesley and "Liam" for marijuana, and was also revealed to be something of a conspiracy theorist.

For five years, Fred spent an arduous life as a "cow," the Pylean equivalent of a slave. The harsh life of solitude and serfdom took a serious toll on her social skills, as well as her mental health. (When Angel meets Fred she is curled up in a cave, scribbling on the already-covered walls. She had seemingly convinced herself that her previous life in LA had not been real. It was revealed that Fred had once been forced to wear an explosive shock collar.) However, Fred's salvation comes when Angel and his crew arrive in Pylea to find Cordelia Chase, who had become trapped there. It is notable that when Angel's demon came fully to the fore, it attacked just about everyone but Fred- including Charles and Wesley. Despite this shocking display of violence, Angel never seemed to scare Fred. When Pylea is liberated, Fred accompanies Angel and the rest of the gang back to Los Angeles and stays in the Hyperion Hotel to re-adjust to life on Earth and regain her mental stability. Despite several traumatic instances, such as being held hostage by Gunn's old vampire-hunting crew, she adjusts quite well to "normal" life. Her knowledge of physics and mathematics make her an excellent asset when researching and developing strategies. Fred quickly develops a romantic relationship with Gunn, which lasts roughly one year. She is also the object of affection of Wesley Wyndam-Pryce, who attempts to step aside after Gunn and Fred started dating, but is still drawn to her. Near the end of her relationship with Gunn, Fred and Wesley share a kiss, but after discovering that Wesley had been in a relationship with Lilah Morgan, her feelings for Wesley cool.

Eventually, Fred discovers that it was actually her former professor's fault that she had been trapped in Pylea, and indeed, Professor Seidel had attempted to trap her in another world again. Furious, she plots to kill him, with Wesley's help. Gunn, however, feels that such a brutal act, even against Seidel, will ultimately destroy her, and as a result, in a battle where she is trying to kill him and she is trying to trap him in a hell dimension, Gunn snaps Seidel's neck himself and drops the body into the portal. Unfortunately, this causes a rift between Fred and Gunn, and ultimately ends their relationship.

However, everything changes for Fred when she and the rest of Angel's crew joins Wolfram & Hart. Her memory is altered by a spell and it is unclear how much of Seasons 3 and 4 she remembers differently or at all (everything specific to Angel's son Connor is certainly lost). Fred receives her own laboratory and becomes the head of Wolfram & Hart's Science Division. A major asset to the team, Angel consistently relies on her department to quickly and efficiently solve problems. After going on a few dates with co-worker Knox, Fred begins to have feelings for Wesley again. The two pair for about a week, but the couple's happiness is not to last.

A mysterious sarcophagus, allowed through customs by a signature from Gunn, appears in the lab. As Fred examines it, a hole opens in the cover and a breath of wind blows into her face. It turns out that the sarcophagus is a holding cell for Illyria, one of the original, pure-breed demons known as the Old Ones, which is predestined to rise again. The air Fred inhales is actually Illyria's essence, which immediately begins a parasitic existence in her body, eating away at it and making her a shell. Worse still, Knox had worshipped Illyria for years and worked at Wolfram & Hart for the sole purpose of bringing the demon back. Because of his affections for Fred, he chose her as the only one "worthy" to house his god.