Kingsolver was born in Annapolis, Maryland, in 1955 and grew up in Carlisle, Kentucky. When Kingsolver was seven years old, her father, a physician, took the family to Léopoldville, Congo (now the Democratic Republic of the Congo). Her parents worked in a public health capacity, and the family lived without electricity or running water.

After graduating from high school, Kingsolver attended DePauw University in Greencastle, Indiana, on a music scholarship, studying classical piano. Eventually, however, she changed her major to biology when she realized that "classical Pianists compete for six job openings a year, and the rest of [them] get to play 'Blue Moon' in a hotel lobby". She was involved in activism on her campus, and took part in protests against the Vietnam war. She graduated Phi Beta Kappa with a Bachelor of Science in 1977, and moved to France for a year before settling in Tucson, Arizona, where she lived for much of the next two decades. In 1980, she enrolled in graduate school at the University of Arizona, where she earned a master's degree in ecology and evolutionary biology.

Kingsolver began her full-time writing career in the mid-1980s as a science Writer for the university, which eventually led to some freelance feature writing, including many cover stories for the local alternative weekly, the Tucson Weekly. She began her career in fiction writing after winning a short story contest in a local Phoenix newspaper. In 1985, she married Joseph Hoffmann; their daughter Camille was born in 1987.

Kingsolver's first novel, The Bean Trees, was published in 1988, and told the story of a young woman who leaves Kentucky for Arizona, adopting an abandoned child along the way; she wrote it at night while pregnant with her first child and struggling with insomnia. Her next work of fiction, published in 1990, was Homeland and Other Stories, a collection of short stories on a variety of topics exploring various themes from the evolution of cultural and ancestral lands to the struggles of marriage.

Her major non-fiction works include her 1990 publication Holding the Line: Women in the Great Arizona Mine Strike of 1983 and 2007's Animal, Vegetable, Miracle, a description of eating locally. She has also been published as a science Journalist in periodicals such as Economic Botany on topics such as desert plants and bioresources.

She moved with her daughter to Tenerife in the Canary Islands for a year during the first Gulf war, mostly due to frustration over America's military involvement. After returning to the US in 1992, she separated from her husband.

Her work often focuses on topics such as social justice, biodiversity and the interaction between humans and their communities and environments. Each of her books published since 1993 has been on the New York Times Best Seller list. Kingsolver has received numerous awards, including the Dayton Literary Peace Prize's Richard C. Holbrooke Distinguished Achievement Award 2011, UK's Orange Prize for Fiction 2010, for The Lacuna, and the National Humanities Medal. She has been nominated for the PEN/Faulkner Award and the Pulitzer Prize.

In 1994, Kingsolver was awarded an Honorary Doctorate of Letters from her alma mater, DePauw University. In the same year, she married Steven Hopp, an ornithologist, and their daughter, Lily, was born in 1996. In 2004, Kingsolver moved with her family to a farm in Washington County, Virginia, where they currently reside. In 2008, she received an Honorary Doctorate of Humane Letters from Duke University, where she delivered a commencement address entitled "How to be Hopeful".

Kingsolver is also a published poet and Essayist. Two of her essay collections, High Tide in Tucson (1995) and Small Wonder (2003), have been published, and an anthology of her poetry was published in 1998 under the title Another America. Her essay "Where to Begin" appears in the anthology Knitting Yarns: Writers on Knitting (2013), published by W. W. Norton & Company. Her prose poetry also accompanied photographs by Annie Griffiths Belt in a 2002 work titled Last Stand: America's Virgin Lands.

Kingsolver has received a number of awards and honors. In 2000, she was awarded the National Humanities Medal by the US President Bill Clinton. Her 1998 bestseller, The Poisonwood Bible, won the National Book Prize of South Africa, and was shortlisted for both the Pulitzer Prize and PEN/Faulkner Award. Her most notable awards include the James Beard Award, the Los Angeles Times Book Prize, the Edward Abbey EcoFiction Award, the Physicians for Social Responsibility National Award, and the Arizona Civil Liberties Union Award. Her novel, The Lacuna, won the 2010 Orange Prize for Fiction. Every book that Kingsolver has written since 1993's Pigs in Heaven has been on The New York Times Best Seller list, and her novel The Poisonwood Bible was chosen as an Oprah's Book Club selection.

Starting in April 2005, she and her family spent a year making every effort to eat food produced as locally as possible. Living on their farm in rural Virginia, they grew much of their own food, and obtained most of the rest from their neighbors and other local farmers. Kingsolver, her husband and her elder daughter chronicled their experiences that year in the book Animal, Vegetable, Miracle. Although exceptions were made for staple ingredients which were not available locally, such as coffee and olive oil, the family grew vegetables, raised livestock, made cheese and preserved much of their harvest.

In a 2010 interview with The Guardian, Kingsolver says, "I never wanted to be famous, and still don't, [...] the universe rewarded me with what I dreaded most". She said she created her own website just to compete with a plethora of fake ones, "as a defence to protect my family from misinformation. Wikipedia abhors a vacuum. If you don't define yourself, it will get done for you in colourful ways".

In 2011, she was awarded the Dayton Literary Peace Prize Richard C. Holbrooke Distinguished Achievement Award. Kingsolver is the first ever recipient of the newly named award to celebrate the U.S. diplomat who played an instrumental role in negotiating the Dayton Peace Accords in 1995. In 2014, she was awarded the Lifetime Achievement Award by the Library of Virginia. The award recognizes outstanding and long-lasting contributions to literature by a Virginian. In 2018 the Library of Virginia named her one of the Virginia Women in History.