[2][3] Strout's first novel, Amy and Isabelle (1998), met with widespread critical acclaim, became a national bestseller, and was adapted into a movie starring Elisabeth Shue.

My Name Is Lucy Barton (2016) was met with international acclaim[7][8][9][4] and topped the New York Times bestseller list.

[11]While teaching part-time at Borough of Manhattan Community College,[14] Strout worked for six or seven years to complete her book Amy and Isabelle, which when published was shortlisted for the 2000 Orange Prize and nominated for the 2000 PEN/Faulkner Award for Fiction.

[11] Amy and Isabelle was adapted as a television movie, starring Elisabeth Shue and produced by Oprah Winfrey's studio, Harpo Films.

[11] Strout was a National Endowment for the Humanities lecturer at Colgate University during the fall semester of 2007, where she taught creative writing at both the introductory and advanced levels.

Ron Charles of The Washington Post summarized her book by saying: "as she did in her bestselling debut, Amy and Isabelle, Strout sets her second novel in a small New England town, whose natural beauty she returns to again and again as this tale unfolds against the background of the Cold War tensions of the 1950s.

[17] The book became a New York Times bestseller and won the Premio Bancarella Award, at an event held in the medieval Piazza della Repubblica in Pontremoli, Italy.

Louisa Thomas, writing in The New York Times, said:The pleasure in reading Olive Kitteridge comes from an intense identification with complicated, not always admirable, characters.

And there are moments in which slipping into a character’s viewpoint seems to involve the revelation of an emotion more powerful and interesting than simple fellow feeling—a complex, sometimes dark, sometimes life-sustaining dependency on others.

A New York Times review noted that Strout "handles her storytelling with grace, intelligence and low-key humor, demonstrating a great ear for the many registers in which people speak to their loved ones," but criticized her for not developing certain characters.

[21] The Washington Post reviewed it with the following observation: "[T]he broad social and political range of The Burgess Boys shows just how impressively this extraordinary writer continues to develop.

Instead, in its careful words and vibrating silences, My Name Is Lucy Barton offers us a rare wealth of emotion, from darkest suffering to—‘I was so happy.

[25] Anything Is Possible was called a "literary mean joke"[24] due to its "hurting men and women, desperate for liberation from their wounds" in contrast to its title.

[25] It was largely seen as an advance on her previous book[7][8][9][4] due to its "ability to render quiet portraits of the indignities and disappointments of normal life, and the moments of grace and kindness we are gifted in response" according to Susan Scarf Merrell of The Washington Post.

The New York Times Book review praised the "intimacy and candor" of Lucy's voice, noting that her halting rhythms resonate.

[32] In 2024, Strout returned to her characters Lucy Barton, Olive Kitteridge, Bob Burgess, and Isabelle Goodrow, now all living in Crosby, Maine, in Tell Me Everything.