Gabaldon was born on January 11, 1952, in Scottsdale, Arizona, United States, the daughter of Jacqueline Sykes and Tony Gabaldon (1931–1998), an Arizona state senator from Flagstaff for sixteen years and later a supervisor of Coconino County. Her father was of Mexican ancestry, and her mother was of English descent.

Gabaldon was the founding editor of Science Software Quarterly in 1984 while employed at the Center for Environmental Studies at Arizona State University. During the mid-1980s, Gabaldon wrote software reviews and technical articles for computer publications, as well as popular-science articles and Disney comics. She was a professor with an expertise in scientific computation at ASU for 12 years before leaving to write full-time.

In 1988, Gabaldon decided to write a novel for “practice, just to learn how” and with no intention to show it to anyone. As a research professor, she decided that a historical novel would be easiest to research and write, but she had no background in history and initially no particular time period in mind. Gabaldon happened to see a rerun episode of the Doctor Who science fiction TV series titled “The War Games.” One of the Doctor’s companions was a Scot from around 1745, a young man about 17 years old named Jamie McCrimmon, who provided the initial inspiration for her main male character, James Fraser, and for her novel’s mid-18th century Scotland setting. Gabaldon decided to have “an Englishwoman to play-off all these kilted Scotsmen,” but her female character “took over the story and began telling it herself, making smart-ass modern remarks about everything.”

Lord John and the Private Matter reached No. 8 on The New York Times Hardcover Fiction Best-Seller List in 2003. In 2007, Lord John and the Brotherhood of the Blade debuted at #1, and the Hand of Devils collection reached No. 24 on The New York Times Hardcover Fiction Best-Seller List. The Scottish Prisoner debuted at #6 on The New York Times E-Book Fiction Best-Seller List in 2011, and the novella A Plague of Zombies was nominated for an Edgar Award by the Mystery Writers of America for the “Best Short Mystery Story” the same year. Reviewing the Lord John series, Publishers Weekly said that “Gabaldon’s prose is crisply elegant” and that she “brings an effusive joy to her fiction that proves infectious even for readers unfamiliar with her work or the period.”

Gabaldon’s Outlander won the Romance Writers of America’s RITA Award for Best Romance of 1991. A Breath of Snow and Ashes (2005) debuted at #1 on The New York Times Hardcover Fiction Best-Seller List and won the Quill Award for Science Fiction/Fantasy/Horror. In 2007, The Montreal Gazette noted that Gabaldon’s books “are in demand in 24 countries in 19 languages,” and that the author “continues to churn out one bestseller after another.” By 2012 her novels had been published in 27 countries and 24 languages.

In 2010 Gabaldon adapted the first third of Outlander into The Exile: An Outlander Graphic Novel, illustrated by Hoang Nguyen. The same year, a 14-song cycle based on Outlander was released under the title Outlander: The Musical.

As of 2014, the Outlander series comprises eight published novels. The eighth installment, Written in My Own Heart’s Blood, was released on June 10, 2014. Gabaldon also published The Exile (An Outlander Graphic Novel) in 2010. The Lord John series is a spin-off from the Outlander books, centering on a secondary character from the original series.

A television adaptation of the Outlander series premiered on Starz in the US on August 9, 2014. Gabaldon made a cameo appearance as Iona MacTavish in the August 2014 episode “The Gathering”. Gabaldon is a paid consultant for the show, and wrote the screenplay for the 2016 season 2 episode “Vengeance Is Mine”.