House was born and grew up in rural Lily, Laurel County, Kentucky, but he also spent much of his childhood in nearby Leslie County, Kentucky, which he has cited as the basis for the fictional Crow County, which serves as the setting for his first three novels. He has degrees from Sue Bennett College (Associate's), Eastern Kentucky University (BA in English with emphasis on American literature), and from Spalding University (Master of Fine Arts in Creative Writing). In 2000, House was chosen, along with since-published authors Pamela Duncan, Jeanne Braselton and Jack Riggs, as one of the ten emerging talents in the south by the Millennial Gathering of Writers at Vanderbilt University.

House's first novel, Clay's Quilt, was published in 2001. It appeared briefly on the New York Times Best Seller list and became a word-of-mouth success throughout the Southern United States. It was a finalist for both the Southeast Booksellers' Association fiction award and the Appalachian Writers' Association Book of the Year Award. He followed with A Parchment of Leaves (2003), which became a national bestseller and was nominated for several major awards. The book was a finalist for the Southern Book Critics' Circle Prize and won the Award for Special Achievement from the Fellowship of Southern Writers, the Chaffin Award for Literature, the Kentucky Novel of the Year Award and many others.

House's next book, The Coal Tattoo (2004), was a finalist for the Southern Book Critics' Circle Prize as well as winning the Appalachian Writers' Association Book of the Year Award, the Kentucky Novel of the Year Award, and others. House's work has been championed by such acclaimed writers as Lee Smith and Larry Brown, who were both mentors for House.

In March 2009, House published Something's Rising with fellow anti-mountaintop removal activist Jason Howard. The book is a series of profiles of various anti-mountaintop removal activists from the region, including musician Jean Ritchie, author Denise Giardina, and activist Judy Bonds. The book was called "revelatory" by esteemed author and oral historian Studs Terkel, in his last blurb. Lee Smith wrote the introduction.

House's fourth novel, "Eli the Good," was published in September 2009 to great acclaim. The book emerged as a number one bestseller on the Southern lists and received the first annual [Storylines Prize] from the New York Public Library system, an award given to a book for use in the ESL and literacy programs of New York City.

House's writing has appeared in Oxford American, Newsday, Bayou, The Louisville Review, Night Train, Appalachian Heritage, Wind and other publications. His work has been nominated for two Pushcart Prizes and anthologized in such books as New Stories From the South: The Year's Best, 2004. He has also written the introductions to Missing Mountains, a study of mountaintop removal; From Walton's Mountain to Tomorrow, a biography of Earl Hamner, Jr., and Gregory of Nyssa's Life of Moses, a new edition by HarperCollins.

In 2005, House wrote the play The Hurting Part, which was produced by the University of Kentucky. In 2009 his second play, "Long Time Travelling," was produced by the Actor's Guild of Lexington (Kentucky).

House served as a writer in residence at Eastern Kentucky University 2004-2005 and at Lincoln Memorial University 2005-2010. At LMU he also directed the Mountain Heritage Literary Festival. In 2010 House became the NEH Chair in Appalachian Studies at Berea College in Berea, Kentucky. He has served on the fiction faculty at Spalding University's MFA in Creative Writing since 2005.

In 2010 House was selected as the focus of the Silas House Literary Festival at Emory and Henry College in Emory, Virginia. The same year he was chosen as Appalachian Writer of the Year by Shepherd University in Shepherdstown, West Virginia.

House is also a music journalist and a contributing editor to No Depression magazine, for which he has written features on Lucinda Williams, Delbert McClinton and many others. House is also an in-demand press kit writer for Nashville's music business, having written biographies for such artists as Kris Kristofferson, Buddy Miller, Del McCoury and Leann Womack. In 2001 and 2002, he was a regular contributor to NPR's All Things Considered.

Since 2005 House has been increasingly visible in the fight against mountaintop removal mining, an environmentally devastating form of coal mining that blasts the entire top off a mountain and fills the valley below with the debris. House wrote the original draft of the 2005 Kentucky authors' statement against the practice; since the draft more than three dozen authors have signed it. House has published many articles about mountaintop removal as well as performing at various concerts as a member of Public Outcry, an acoustic band formed for the purpose of raising awareness of mountaintop removal mining. The other members of the group are authors George Ella Lyon and Anne Shelby, with musicians Jason Howard, Jessie Lynne Keltner and Kate Larken. Public Outcry tours college campuses to educate students about mountaintop removal. House and Howard also perform together as The Doolittles.

House has been joined in this fight by other important Kentucky writers such as those who are members of Public Outcry as well as Wendell Berry, Bobbie Ann Mason and Maurice Manning.

House has recently finished editing the posthumous manuscript of poet and novelist James Still, one of House's literary idols. House is currently at work on his fifth novel and a play. He recently co-wrote a screenplay for actress Ashley Judd that has not yet been produced. House resides in London, Ky. with his two daughters.