In 1962, White graduated from Warner Pacific College. That same year, he married his wife Lyla. They had two children, one of whom is the actor/comedian and screenwriter Mike White.

After receiving his B.A. from Warner Pacific College, then graduating with an M.A. in communications from the University of Portland, White followed with graduate work in communications and film at University of Southern California, UCLA, and Harvard. He received his Doctorate of Ministry from, and was a professor of communications and preaching for over a decade at, Fuller Theological Seminary. During this time he also worked as an evangelical pastor.

After their marriage, Mel White admitted to his wife that he had always been attracted to men. He embarked on a long process of attempted cures for his homosexuality, including psychotherapy, prayer, electroconvulsive therapy, and exorcism. None of these techniques changed his homosexuality, and after he attempted suicide, he and his wife agreed to an amicable divorce. His son Mike is bisexual.

In 1984, White began dating Gary Nixon. In June 2008 they were legally married in California. They currently reside in Lynchburg, Virginia.

In 1994, White wrote his autobiography, To Be Gay And Christian In America, which detailed his former career in the Religious Right and his struggle coming to terms with his sexuality. His former wife wrote the foreword to this book.

After coming out, White transferred his clergy credentials to the gay-affirming Metropolitan Community Church.

In 1997, White was awarded the American Civil Liberties Union's National Civil Liberties Award for his efforts to apply the "soul force" principles of Mahatma Gandhi and Martin Luther King Jr. to the struggle for justice for sexual minorities. He founded Soulforce, a national social justice organization that works to end the political and religious oppression of LGBT people, in 1998.

He produced, wrote, and directed 53 documentary films and television specials on spirituality. He is also an author; among his 16 books (nine bestsellers), he wrote about the Philippines' Ninoy and Corazon Aquino (Aquino), the Jonestown tragedy (Deceived), David Rothenberg, a child burned by his father (David), Lust the Other Side of Love, and talk-show host/producer Mike Douglas (When the Going Gets Tough).

Recently, White appeared on the fourteenth season of The Amazing Race along with his son Mike. The two lasted for seven legs on the race before being eliminated in sixth place in Phuket, Thailand. Mel is also a contributor to the popular DVD program Living the Questions, an introduction to Progressive Christianity.

White ghostwrote several books for fellow evangelicals, including Billy Graham (Approaching Hoofbeats), Pat Robertson (America's Date with Destiny), and Jerry Falwell (Strength for the Journey and If I Should Die Before I Wake). White began coming out privately during the same period that the Religious Right stepped up its anti-homosexual statements.

Since 1993, he has devoted himself full-time to minister to lesbians, gays, bisexuals, and transgender people, working on their behalf in the media, in the political process, and with fellow religious leaders.

White's autobiography, Stranger at the Gate: To be Gay and Christian in America (1994), is still being read widely, especially by LGBTQ people, their families and friends struggling to reconcile faith with sexual orientation. White's latest book, Religion Gone Bad: Hidden Dangers from the Christian Right (2007), is called "A consciousness-raising, must-read book" by Bishop John Shelby Spong.