Piper is the founder and senior teacher of desiringGod.org, named for his book Desiring God: Meditations of a Christian Hedonist (1986), and has written a number of award-winning books, including ECPA Christian Book Award winners Spectacular Sins,What Jesus Demands from the World,Pierced by the Word, and God's Passion for His Glory, as well as bestsellers Don't Waste Your Life and The Passion of Jesus Christ.
According to Piper, he had a religious conversion at his mother's knee while on a family vacation in Florida when he was six years old. Piper has remarked that the fact he was converted at the age of six "blows him away", not because he remembers the event, but due to his belief in the Bible's telling of the hopeless condition of all humans who have not been converted.
Piper married Noël Henry in December 1968, and together they have four sons, a daughter, and twelve grandchildren. He attended Wheaton College between 1964 and 1968, majoring in literature and minoring in philosophy. Studying romantic literature with Clyde Kilby led him to take particular interest in poetry, Piper has published several books of poetry, and continues to pursue, with his poetry, the deeper reality of personal, theological  and social  reality. He has explained in both prose and poetry why he writes.C. S. Lewis has remained a profound influence in Piper's life, in large measure, he says, because of the combination of rational precision with language, and profound poetic perception of reality.
At the end of his sophomore year Piper thought he had clarity about his future as a medical doctor. That changed dramatically and suddenly in the fall of 1966 as he lay in the college infirmary for three weeks with mononucleosis. During those weeks he listened to WETN, the college radio station, to the fall chapel messages by Harold John Ockenga, Pastor of Park Street Church, Boston. Piper has written that he dates his decisive call to the ministry of God’s word to that experience: “I can remember listening there on my bed to his messages on the radio and feeling inside my heart simply explode with longing to be able to handle the word of God the way he was handling it in the pulpit at Edman Chapel. Before those three weeks were over, I had resolved to drop organic chemistry. . . That was, I believe, my call to the ministry of the word.”
But the most formative season theologically was yet to come: three years under the tutelage of Daniel Payton Fuller, at Fuller Theological Seminary in Pasadena, California, from 1968 to 1971. Fuller’s influence on Piper was, he admits with thankfulness, enormous. Three things that would mark Piper’s life-work are traceable to that influence: assiduous attention to exegetical detail in Bible study (indeed in all reading), a central conviction of the all-embracing sovereignty of God, and what Piper came to call Christian Hedonism.
John Piper teaching at VMware, Palo Alto, California in February 2020.
In 1980, Piper became pastor of Bethlehem Baptist Church in Minneapolis, Minnesota, where he ministered until March 31, 2013 as pastor for preaching and vision. Piper became involved in evangelical Christianity following the publication of his book Desiring God: Meditations of a Christian Hedonist in 1986, and has continued to publish dozens of books further articulating his theological perspective. In 1994, Piper founded Desiring God Ministries, with the aim of "spread[ing] a passion for the supremacy of God in all things for the joy of all peoples through Jesus Christ". Desiring God Ministries offers all of Piper's sermons and articles from the past three decades—and most of his books—online at no cost.
Piper took an eight month leave of absence from his ministry from May 1, 2010, to January 9, 2011. He announced in June 2011 that he would soon step down from his role of pastor. A candidate to succeed him was announced in March 2012, and on May 20, 2012, Jason Meyer was voted in (784 yes to 8 no) to be the next pastor for preaching & vision, replacing Piper.
On March 31, 2013 (Easter Sunday), Piper preached his final sermon as pastor of Bethlehem Baptist and announced in an open letter to the congregation that he and his family would be moving to Tennessee for at least a year, in order for the church's new leadership to develop a strategic vision for the church without distractions. He still attends the church and is designated pastor emeritus with no official role in the church leadership.
He married Noël Henry in 1968 and had five children, including an adopted daughter. His son Abraham Piper has publicly criticized evangelical Christianity.
On January 11, 2006, Piper announced that he had been diagnosed with prostate cancer. According to a letter sent to his church, he and his doctors believed that the cancer was fully treatable. Piper responded to his diagnosis with the following:
This news has, of course, been good for me. The most dangerous thing in the world is the sin of self-reliance and the stupor of worldliness. The news of cancer has a wonderfully blasting effect on both. I thank God for that. The times with Christ in these days have been unusually sweet.
Piper underwent successful surgery on February 14, 2006.