Piper was born in Chattanooga, Tennessee, to Bill and Ruth Piper. His father was a traveling evangelist and church planter. When he and his older sister were still young, the Pipers moved to Greenville, South Carolina, where he spent the remainder of his youth and graduated from Wade Hampton High School.
At six years old, Piper was converted to faith in Christ at his mother's knee while on vacation in Florida. He remarks that it "blows him away" that he was saved at six years old, not because he remembers the event, but because the Bible tells him what happened to him. When he shared his testimony on his website, desiringgod.org, he said that it's very dangerous to rely on one's memory or experience when pondering when God saved them. He states this is the case, because both are fallible and can be misleading. Thus, he wants to encourage others like himself who can't remember the exact date of their conversion, by pointing them to what the Bible says.
Piper attended Wheaton College (1964–68) majoring in literature and minoring in philosophy. Studying romantic literature with Clyde Kilby stimulated his poetic side, and today he regularly composes poetry to celebrate special family occasions as well as annually composing story-poems (based on the life of biblical characters) for his congregation during the four weeks of Advent.
In college, he was originally on the pre-medicine track, only to decide to go into ministry during a bout of sickness, while listening to the sermons of Harold Ockenga over the radio from his hospital bed. He then completed a Master of Divinity degree at Fuller Theological Seminary in Pasadena, California. While at Fuller, he took several courses from Daniel Fuller and through him discovered the writings of Jonathan Edwards. Along with C. S. Lewis, Edwards and Fuller are noted influences in Piper's life and ministry.