Prior to becoming a leading figure in the Christian countercult movement, Hanegraaff was closely affiliated with the ministry of D. James Kennedy of Coral Ridge Presbyterian church in Florida. During his association with Kennedy in the 1980s, Hanegraaff applied memory-based techniques (such as acrostic mnemonics) to summarise strategies, methods and techniques in Christian evangelism. His work bears resemblances to memory dynamics techniques developed in speed-reading courses and in memory training programs used in some executive business courses.

During the late 1980s Hanegraaff became associated with Walter Martin (1928-1989) at the Christian Research Institute (CRI), the conservative Protestant countercult and apologetic ministry which Martin founded in 1960.

After Martin's death from heart failure in June 1989, Hanegraaff became president of CRI. As part of his role as ministry president, Hanegraaff assumed the role from Martin of anchorman on the radio program The Bible Answer Man. Hanegraaff also became a conference speaker and itinerant preacher in churches, pursuing the general ministry charter of CRI. Shortly after the release of Dan Brown's novel, he co-authored The DaVinci Code: Fact or Fiction? with Lutheran apologist Paul Maier. His most recent publication to date is Christianity in Crisis 21st Century, from Thomas Nelson in 2009.

The content of The Bible Answer Man show includes answering questions about Christian doctrine, biblical interpretation, and denominational particularities, as well as special focuses on particular issues when a notable figure is a guest, such as frequent shows focused on Mormonism when former Mormons appear in studio as guests to speak from their experiences.

Christian Research Institute

During his tenure at Christian Research Institute, a rift between Hanegraaff and the family of the late Martin grew amid accusations of changing CRI's mission, and the improper use of its not-for-profit status. In 2003, an audit by Evangelical Council for Financial Accountability found financial irregularities at the CRI, resulting in a "significant reimbursement."

2007 Defamation Suit

Hanegraaff filed a defamation suit against a longtime critic William Alnor for statements made in a fundraising letter alleging mail fraud. The lawsuit was thrown out, the court finding that Hanegraaff did not prove "actual malice.”

Despite its warm reception by evangelicals, the book (as well as Christianity in Crisis) was harshly criticized by many Pentecostal and charismatic leaders such as Don Williams, William DeArteaga and Michael L. Brown.

Worldwide Church of God

Throughout the 1990s, Hanegraaff engaged in dialogue with Joseph Tkach, Jr. and other leaders of the heterodox Worldwide Church of God (WCG), now known as Grace Communion International (GCI). The WCG was founded in the 1930s by Herbert W. Armstrong, and had long been regarded as a cult by evangelicals, primarily for its denial of the Trinity and other traditional Christian doctrines. Following Armstrong's death in 1986, the group re-evaluated many of its teachings, including the British Israel doctrine and various eschatological predictions.

Hanegraaff was one of a handful of evangelical apologists — along with, e.g., Ruth A. Tucker (author of Another Gospel), and members of the White Horse Inn — who assisted in the reforms. The biggest changes, and certainly those most necessary to ensure their acceptance among evangelicals, were in accepting the doctrine of the Trinity and Salvation by Grace through Faith.

The story is told in the 1997 book Transformed by Truth by Joseph Tkach, with a foreword by Hanegraaff. The book, now out of print, is posted chapter by chapter on the GCI Web site.

Hanegraaff has also defended the historicity of the Resurrection of Christ in print and on radio, and has been outspoken against the theory of Evolution, in favour of creationism.

Hanegraaff is noted for his belief that Biblical inerrancy can be proven on a rational basis. He has also followed his predecessor, Walter Martin, in opposing what he describes as "pseudo-Christian" cults, such as the Jehovah's Witnesses, and Mormons. In recent times he has co-authored three novels with Sigmund Brouwer.

Word-Faith movement

In his 1993 book Christianity in Crisis, Hanegraaff charged the Word-Faith movement with heretical teachings, saying that many of the Word-Faith groups were "cults", and that those who "knowingly" accepted the movement's theology were "clearly embracing a different gospel, which is in reality no gospel at all."

He made much of the Faith teachers' alleged tendencies to rely on visions and other experiential phenomena rather than Scripture alone.

Counterfeit Revival

Hanegraaff revisited some of the same issues in his 1997 book Counterfeit Revival, in which he rejected the claims of many Pentecostal and charismatic teachers such as Rodney Howard Browne concerning what became known as the Toronto Blessing. The Toronto Blessing was associated with the Vineyard church located near the Toronto airport, and was characterized by spontaneous and sustained outbursts of bodily phenomena such as laughing, crying, animal noises, and dancing. The proponents of this blessing believed this was a special time of refreshing bestowed on churches by the Holy Spirit. A different set of phenomena and claims subsequently emanated from churches in Brownsville, Pensacola, Florida, and became known as the Brownsville Revival.

Counterfeit Revival was criticized in Christianity Today magazine's review of the book. The review, while acknowledging that Counterfeit Revival "exposes some real excesses and imbalances" in the Toronto Blessing, also states that Counterfeit Revival is a "misleading, simplistic, and harmful book, marred by faulty logic, outdated and limited research".