Meyer attended Baltimore city public schools, including Baltimore City College High School, until dropping out at age 16 and getting a GED. He spent the next five years working as a bicycle mechanic and occasionally volunteering at Baltimore’s Shock Trauma Center.

At age 20, while taking college classes in Baltimore, Meyer decided to become a writer. He also decided to leave his hometown and at 22, after several attempts at applying to elite colleges, was admitted to Cornell University. Meyer graduated Cornell with a degree in English but then took a job on Wall Street to pay off his student loans.

With the Swiss investment bank UBS, Meyer trained in London and Zurich and was given a position as a derivative trader. After several years at UBS, he had written most of a novel (no relation to American Rust) and decided to pursue his dream of becoming a writer. When attempts at publishing that novel failed, a book he has called “an apprentice-level work,” Meyer took jobs as an emergency medical technician and construction worker. He was preparing for a long-term career as a paramedic when, in 2005, he received a fellowship at the Michener Center for Writers in Austin, Texas, where he wrote the majority of American Rust.

Not long after arriving in Austin, Meyer drove to New Orleans to do relief work during Hurricane Katrina. He arrived in the middle of the hurricane and spent several days doing emergency medical work for a local police department.

In 2010, Meyer was named in the New Yorker's list '20 under 40', their once every decade list of the 20 writers under the age of 40 that it feels are tipped for great things.

American Rust was a winner of the 2009 Los Angeles Times Book Prize. It was an Economist Book of the Year in 2009, a Washington Post Top Ten Book of 2009, a New York Times Notable Book of 2009, on Newsweek's List of "Best. Books. Ever.", a Pittsburgh Post-Gazette Best Book of 2009, an Idaho Statesman Top Book of 2009, a Kansas City Star Top 100 Book of 2009, a Daily Beast Favorite Book of 2009, and an Amazon Top 100 Book of 2009. Reviewers in the UK's Telegraph, Cleveland Plain-Dealer, and Dayton Daily News have suggested it fits the category of "Great American Novel." The bulk of American Rust was written during Meyer’s time at the Michener Center (2005-2008). In December 2007 an early version of American Rust was acquired by Spiegel & Grau, a Random House imprint. Between December 2007 and May 2008, Meyer made significant changes to the manuscript, lengthening the book by 30%. Further significant changes were made between the version published as the advanced readers copy (based on the May 2008 manuscript) and the final hardback (based on changes made between May 2008 and October 2008). American Rust has been bought by publishers in sixteen countries and scheduled for translation into eleven languages. It is a third person, stream-of-consciousness narrative influenced, according to Meyer, by writers such as James Joyce, William Faulkner, Virginia Woolf, and James Kelman. While a reviewer in The Baltimore Sun compared the novel to the work of Faulkner, various other reviewers, including Michiko Kakutani of The New York Times, Ron Charles of The Washington Post, and Taylor Antrim writing in The Daily Beast, have favorably compared Meyer to a wide variety of more traditional writers, including Cormac McCarthy, Ernest Hemingway, John Steinbeck, J.D. Salinger, and Dennis Lehane.

Meyer currently lives with his wife in Austin, TX.