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.
He married Noël Henry in 1968, and together they have four sons, a daughter, and twelve grandchildren.
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.
His mother died in December 1974 in a bus wreck in Israel. Piper's 1990 booklet What's the Difference? included a tribute to her. His father died on March 6, 2007.
In 1980, Piper became Pastor of Bethlehem Baptist Church in Minneapolis, Minnesota, where he ministered until March 31, 2013. Piper hit the evangelical scene after the publication of his book Desiring God: Meditations of a Christian Hedonist (1986) and has continued to publish dozens of other books further articulating this theological perspective. In 1994, he founded Desiring God Ministries, which provides all of Piper's sermons and articles from the past three decades, and most of his books online free of charge, as well as offering for sale books, CDs, and DVDs and regularly hosting conferences.
According to Piper, Desiring God Ministries exists to "spread a passion for the supremacy of God in all things for the joy of all peoples through Jesus Christ," which is also his personal motto. Piper calls those who live out this motto Christian Hedonists.
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.
In August 2009, Piper claimed that a small tornado occurring during a conference of the Evangelical Lutheran Church of America was a "gentle but firm warning" from God. He wrote a blog post tying the storm to the ELCA's consideration of its position on issues concerning homosexuality.
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 aimed to step down from his role as pastor in June 2014. A candidate to succeed him was announced in March 2012.
On May 20, 2012 Jason Meyer was voted in (784 Yes to 8 No) to be the next Pastor for Preaching & Vision, replacing John Piper.
On March 31, 2013 (Easter Sunday), he 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 so that the new leadership can develop a strategic vision for the church without distractions.
Piper advocates Christian hedonism and teaches that "God is most glorified in us when we are most satisfied in Him" and that God's highest pursuit ("his glory") and man's deepest and most durable happiness come together in one pursuit—namely, the pursuit of joy in God.
Piper holds to a complementarian view of gender roles. This view says that the Bible teaches that a husband is called to lovingly lead, protect and provide for his wife and family, and that the wife should joyfully and intelligently affirm and submit to her husband's leadership. He also says that the Bible teaches that men are to bear the primary responsibility to lead the church and that therefore only men should be elders. Piper along with Wayne Grudem was co-editor of one of the bedrock books in this area, called Recovering Biblical Manhood and Womanhood. One of the chapters has been reprinted several times as an independent short book called What's the Difference?.
Piper believes in justification by faith alone apart from any works, and his teachings emphasize the need for the active and inevitable perseverance of the believer in faith, sanctification, and enduring sufferings, which he believes is evidence of God's saving grace. According to Piper, a once-professing Christian who does not faithfully persevere until the end demonstrates that he was mistaken about his election and was never a true believer in the first place.
Regarding spiritual gifts, Piper is a continuationist. That is, he believes that supernatural gifts such as prophecy, miracles, healings, and speaking in tongues have not ceased and should be sought by the church, in particular with regard to missions and evangelism. He does believe, however, that the office of apostle has ceased and that the gift of prophecy in the church is not the same as the inspiration of scripture. While he believes that God's supernatural revelation in the N.T. gift of prophecy is without error, he says that today, outside the Biblically recorded Word of God, the prophet's perception, understanding and delivery of that revelation is imperfect and fallible, thus modern prophecies within the church are subject to sifting.
Piper teaches that God has only one covenant people, mostly believing Jews in the Old Testament, and now that relationship has been superseded by the Church. Thus, all Christians, both Jew and Gentile, are the rightful inheritors of all the promises made to ethnic Israel (land, kingdom, etc.), and Jews who reject Jesus as Messiah have no divine right of claim on those promises.
Love Your Enemies: Jesus' Love Command in the Synoptic Gospels and the Early Christian Paraenesis (Cambridge University Press, 1980; Baker, 1991).
The Justification of God: An Exegetical and Theological Study of Romans 9:1–23 (Baker, 1983; 2nd edition 1993).
^"Jesus chose Twelve Apostles for a unique, unrepeatable role in the history of redemption... there seem to be also another group (or groups) of men called and authorized by Jesus in the New Testament, some of whom are on a par with the Twelve in their teaching authority. Paul certainly believed that his call and commission by the risen Christ put him on a par with the Twelve in his teaching role..." 
^"But the spiritual gift of prophecy is different from the inspiration of Scripture." 
^"God reveals something to the mind of the prophet (in some way beyond ordinary sense perception), and since God never makes a mistake, we know that his revelation is true. It has no error in it. But the gift of prophecy does not guarantee the infallible transmission of that revelation. The prophet may perceive the revelation imperfectly, he may understand it imperfectly, and he may deliver it imperfectly."
^"We need a third category for the "spiritual gift of prophecy"—Spirit-prompted, Spirit-sustained, revelation-rooted, but mixed with human imperfection and fallibility and therefore in need of sifting."