At 21, Miller left his home in Houston, Texas and traveled across the country to Portland, Oregon, a place where he put down roots as he had planned when he started his road trip a few months before. Miller's first book, Prayer and the Art of Volkswagen Maintenance (Harvest House Publishers 2000), chronicled the cross-country road trip he took at age 21. It was printed with little fanfare, but it was republished more successfully in 2005 as Through Painted Deserts. During this time, Miller was the editor of an online Christian magazine called roadsearching.com and the owner of a small Portland-based publishing company called Coffee House Books, which published home schooling textbooks. Miller became a New York Times Bestselling Author when he published Blue Like Jazz in 2003. In 2004, Miller released Searching For God Knows What, which explores how the life of Jesus illustrates the human personality. In 2006, he added another book, To Own A Dragon, which offered Miller's reflections on growing up without a father. This book reflected an interest already present in Miller's life, as he founded the Mentoring Project (formerly the Belmont Foundation), a non-profit that partners with local churches to mentor fatherless young men. Don's next book, A Million Miles in a Thousand Years, was released in late 2009. Later that year, Miller began production of All Things Converge http://www.allthingsconverge.com/ ...a series of DVDs for small groups that feature Miller interviewing prominent Christian writers and theologians. The first three DVDs in the series were released in the fourth quarter of 2009.

Miller also serves as the Founding Director of The Burnside Writers Collective, a group of spiritual writers who contribute to an online magazine.

Miller is recognized for his feelings that Christian faith should be a relationship, rather than a formula. He writes in Searching for God Knows What that too many Christians act like the Bible is a sort of math textbook, rather than a long story of God's involvement with people through friendships with Biblical figures like Adam, Abraham, and Moses. This emphasis on the Bible as a narrative has made his writings popular with many involved in the emerging church conversation. Miller does not consider himself a follower of the movement; he still recognizes the need of mankind to recognize its depravity so that it might better teach the concept of love.

On March 2, 2007, during an interview on the Relevant Magazine podcast, he revealed that he has been working on a screenplay with Steve Taylor.On Don Miller's website http://www.donmilleris.com/ he further discusses the screen play noted above.

Miller delivered the first night's closing prayer at the 2008 Democratic National Convention on August 25, 2008.

Miller serves on President Barack Obama's Task Force on Fatherhood and Healthy Families.