Sproul holds degrees from Westminster College, Pennsylvania (B.A., 1961), Pittsburgh-Xenia Theological Seminary (M.Div, 1964), the Free University of Amsterdam (Drs., 1969), and Whitefield Theological Seminary (Ph.D., 2001). He had to learn the Dutch language while studying in the Netherlands which he has described as a trying experience. He has taught at numerous colleges and seminaries, including Reformed Theological Seminary in Orlando and Jackson, Mississippi, and Knox Theological Seminary in Ft. Lauderdale.

Currently, Sproul is Senior Minister of Preaching and Teaching at Saint Andrew's Chapel in Sanford, Florida. He was ordained as an elder in the United Presbyterian Church in the USA in 1965, but left that denomination because of liberalism around 1975 and joined the Presbyterian Church in America. (St. Andrew's Chapel, however, is independent and not affiliated with that or any other denomination.) He is also a Council member of the Alliance of Confessing Evangelicals.

Sproul has been an ardent advocate of Calvinism in his many print, audio, and video publications, and he is also known for his advocacy of the Thomistic and Evidentialist approaches to Christian apologetics and his rejection of presuppositionalism. A dominant theme in many of Sproul's Renewing Your Mind lessons is the holiness and sovereignty of God.

Sproul was a critic of the 1994 ecumenical document Evangelicals and Catholics Together.

Sproul's work The Holiness of God (ISBN 0-8423-3965-5) is considered a modern classic on the subject of God's character, and his book Not a Chance: The Myth of Chance in Modern Science and Cosmology (ISBN 0-8010-5852-X) was highly praised by those who reject the materialism advocated by some in the scientific community.

Through Ligonier Ministries and the Renewing Your Mind radio program and conferences, Sproul has generated an extensive collection of audio and video lectures on subjects such as the history of philosophy, theology, Bible study, apologetics, intelligent design, and Christian living. In addition, Sproul is a prolific author who has written more than 60 books and many articles for evangelical publications. He signed the 1978 Chicago Statement on Biblical Inerrancy, which affirmed the traditional view of Biblical inerrancy, and he wrote a commentary on that document titled Explaining Inerrancy. He also served as the editor of the Reformation Study Bible (ISBN 0-87552-643-8), a six year long project, which has appeared in several editions and was also known as the New Geneva Study Bible.

In 2006 Ligonier Ministries launched Reformation Trust Publishing to produce books true to the historic Protestant Christian faith by today's best Reformed pastors, educators, and church leaders.

Some of Sproul's other written works include:

• Holy, Holy, Holy: Proclaiming the Perfections of God, Reformation Trust Publishing, 2010 - 978-1-56769-205-1
• Who is Jesus?, Reformation Trust Publishing, 2009 - Crucial Questions series 978-1-56769-181-8
• Can I Trust the Bible?, Reformation Trust Publishing, 2009 - Crucial Questions series 978-1-56769-182-5
• How Should I Live in This World?, Reformation Trust Publishing, 2009 - Crucial Questions series 978-1-56769-180-1
• Can I Know God's Will?, Reformation Trust Publishing, 2009 - Crucial Questions series 978-1-56769-179-5
• Does Prayer Change Things?, Reformation Trust Publishing, 2009 - Crucial Questions series 978-1-56769-178-8
• The Prayer of The Lord, Reformation Trust Publishing, 2009 978-1-56769-118-4
• The Prince's Poison Cup, Reformation Trust Publishing, 2008 978-1-56769-104-7
• Five Things Every Christian Needs to Grow, revised, expanded Reformation Trust Publishing, 2008 978-1-56769-103-0
• The Truth of the Cross, Reformation Trust Publishing, 2007 978-1-56769-087-3
• A Taste of Heaven, Reformation Trust Publishing, 2006 ISBN 978-1-56769-076-7
• The Lightlings, a children's title, Reformation Trust Publishing, 2007 ISBN 978-1-56769-078-1
• Knowing Scripture, InterVarsity, 1977 (ISBN 0-87784-733-9)
• If there is a God, why are there atheists?: A surprising look at the psychology of atheism, Bethany Fellowship, 1978 (ISBN 0-87123-238-3)
• Reason to Believe: A Response to Common Objections to Christianity, Zondervan, 1982 (ISBN 0-310-44911-1)
• Classical Apologetics with John Gerstner and Arthur Lindsley, Zondervan, 1984 (ISBN 0-310-44951-0)
• Abortion: A Rational Look at an Emotional Issue, Navpress, 1990 (ISBN 0-89109-345-1)
• Lifeviews: Make a Christian Impact on Culture and Society, Revell, 1990 (ISBN 0-8007-5357-7)
• Chosen by God, Tyndale, 1994 (ISBN 0-8423-1335-4)
• The Mystery of the Holy Spirit, Tyndale, 1994 (ISBN 0-8423-4378-4)
• Pleasing God, Tyndale, 1994 (ISBN 0-8423-5024-1)
• Now, That's a Good Question!, Tyndale, 1996 (ISBN 0-8423-4711-9)
• Grace Unknown: The Heart of Reformed Theology, Baker, 1997 (ISBN 0-8010-1121-3)
• The Invisible Hand: Do All Things Really Work for Good?, Word Books, 1997 (ISBN 0-8499-1207-5)
• The Priest With Dirty Clothes A Timeless Story Of God's Love And Forgiveness with Liz Bonham (illustrator), Tommy Nelson, 1997 (ISBN 0-8499-1455-8)
• Willing to Believe: The Controversy over Free Will, Baker, 1997 (ISBN 0-8010-6412-0)
• Essential Truths of the Christian Faith, Tyndale, 1998 (ISBN 0-8423-2001-6)
• Renewing Your Mind: Basic Christian Beliefs You Need to Know 3rd ed., Baker, 1998 (ISBN 0-8010-5815-5)
• Faith Alone: The Evangelical Doctrine of Justification, Baker, 1999 (ISBN 0-8010-5849-X)
• Gospel of God: An Exposition of Romans, Christian Focus, 1999 (ISBN 1-85792-490-8)
• The Consequences of Ideas: Understanding the Concepts That Shaped Our World, Crossway, 2000 (ISBN 1-58134-172-5)
• The King Without a Shadow with Liz Bonham (illustrator), P & R, 2000 (ISBN 0-87552-700-0)
• The Last Days According to Jesus, Baker, 2000 (ISBN 0-8010-6340-X)
• Loved By God, W Publishing Group, 2001 (ISBN 0-8499-1648-8)
• The Purpose of God: An Exposition of Ephesians, Christian Focus, 2002 (ISBN 1-85792-609-9)
• Saved from What?, Crossway, 2002 (ISBN 1-58134-417-1)
• The Dark Side of Islam with Abdul Saleeb, Crossway, 2003 (ISBN 1-58134-441-4)
• Defending Your Faith: An Introduction to Apologetics, Crossway, 2003 (ISBN 1-58134-519-4)
• Getting the Gospel Right, Baker, 2003 (ISBN 0-8010-6447-3)
• The Glory of Christ, P & R, 2003 (ISBN 0-87552-703-5)
• The Intimate Marriage: A Practical Guide to Building a Great Marriage, P & R, 2003 (ISBN 0-87552-708-6)
• What's in the Bible: A One-Volume Guidebook to God's Word with Robert Wolgemuth, W Publishing Group, 2003 (ISBN 0-8499-4460-0)
• The Soul's Quest for God: Satisfying the Hunger for Spiritual Communioun with God, P&R Publishing, 2003 (ISBN 0-87552-706-2)
• The Character of God: Discovering the God Who Is, Servant Publications, 2004 (ISBN 0-8307-3398-1)
• Scripture Alone: The Evangelical Doctrine, P & R, 2005 (ISBN 1-59638-010-1)
• What Is Reformed Theology?: Understanding The Basics, Baker, 2005 (ISBN 0-8010-6559-3) - the author describes it as "a shorthand introduction to the crystallized essence of Reformation theology."