In 2371, the Starship Voyager, with Janeway and her crew, was abducted and swept into the distant Delta Quadrant of the galaxy, some 70,000 ligh years form home, where they were essentially stranded. After the destruction of a Maquis ship that had also been abducted to the Delta Quadrant, Janeway accepted the Maquis crew aboard her ship, and invited its commander, Chakotay, to become her second-in-command. Janeway's courage and leadership were instrumental in the survival of her crew as they made the long and difficult journey back to the Alpha Quadrant.

Janeway, whose father was a Starfleet admiral, grew up in Indiana on Earth, where summers were warm and humid. Janeway loved to ski. When she was young, Kathryn's parents took her and her siblings on camping trips, but she never didi like camping, as she was very much a child of the 24th century. Kathryn had a sister, who was the artist of the family. Kathryn loved music, but never learned to play a musical instrument, a fact that she regretted in her adult life. As a child, one of Janeway's heroes was noted 20th century Earth aviator Amelia Earhart. In later years, Janeway would recall that Earhart was one of the inspirations that led her to join Starfleet. Janeway enjoyed tennis when she was in high school, although she did not play the game again until 19 years later when she commanded the Starship Voyager. Janeway was close to her father, and grieved deeply after his tragic accidental drowning in 2358. Early in her career, Janeway served as science officer aboard the U.S.S. Al-Batani. Prior to the Voyager's disappearance, Janeway had been romantically involved with Mark, who took care of Molly, her pet Irish Setter.

During off-duty hours aboard Voyager, Janeway enjoyed participating in a gothic romance holonovel set in the old England on Earth. Captain Janeway was an accomplished pool player. She considered coffee to be an essential part of her lifestyle and had a particular weakness for coffee ice cream. She enjoyed knitting, and in 2372, made a monogrammed blanket for Ensign Samantha Wildman's newborn daughter. The luxury of a hot bath was probably Janeway's favorite form of relaxation.

On stardate 48546, Janeway sought Chakotay's help in experiencing a vision quest in search of her personal animal guide. In 2372, Janeway crossed the Warp 10 barrier, causing her to mutate into an amphibious creature. Fortunately, the Emergency Medical Hologram was able to reverse the mutative process. While mutated, Janeway and Paris mated, producing three amphibian children that they left behind on a planet in the Delta Quadrant.

Janeway became afflicted with a potentially fatal viral disease in 2372 after accidental contact with an insectoid life-form on a planet in the Delta Quadrant. Extensive research determined that the condition could remain benign as long as she remained on the planet, but that she could not survive if she left. Voyager offcier Chakotay was also striken with the disease. Determined that her people should not sacrifice their chance to return home, Janeway ordered her ship to continue their voyage, leaving Janeway and Chakotay behind. On the planet, Janeway (who never particularly enjoyed camping as a child) found life was made more pleasant by Chakotay's support and his wilderness skills. After several weeks, Voyager's crew, with the aid of Vidiian physician Denara Pel were able to obtain an antiviral medication, and they returned to successfully treat Chakotay and Janeway. Chakotay and Janeway grew closer during their time alone together on the planet.

Around stardate 50062, Janeway undertook a Nechani 'ritual of purification' following an accident in which Kes was knocked into a coma after encountering a bio-electric field while investigating a Nechani temple. Following the ritual Janeway returned to the temple with Kes and approached the bio-electric field, upon contact with the field Kes was restored from the coma. The doctor later determined that the 'ritual' had altered the chemical balance of Janeway's blood in such manner that the bio-electric field would not harm her.

On stardate 50126, Janeway was asked by Tuvok to act as a guide in a mind-meld following a hallucination attack triggered by the image of a nebula on the viewscreen. Following several mind-melds during which Tuvok would have the hallucinations Janeway was able to help the doctor trace the cause to a virus Tuvok had contracted during his tour of duty aboard the U.S.S. Excelsior.

On stardate 50518, while returning to Voyager in a shuttlecraft, Janeway and Chakotay was attacked by the Vidiians and crash-land on a planet. Following a subsequent attack on the surface, Janeway was left near death. During this time Janeway believes herself to be caught in a time loop in which the attack repeats, each time with a different situtation but all leading to her eventual death. It is later determined that following the first Vidiian attack that an unknown energy being had occupied part of Janeways brain causing the events to unfold in her mind. With the help of the Doctor and Chakotay the energy being was forced from Janeways brain, restoring her to normal consciousness.