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Duplantis preached his first sermon in 1976. He was introduced by John Hagee as "The Apostle of Joy" on TBN, a phrase that became his professional PR slogan. He has been a full-time evangelistic minister since 1978, using his music and comic talent in his work. In the book "Close Encounters of the God Kind", Duplantis writes about his daily relationship with God, the reality of eternity, perspectives on Heaven and his belief in the depth of the compassion, forgiveness and love God has for humankind.
He is the founder of Jesse Duplantis Ministries (JDM), which maintains an international headquarters in America and branches in the United Kingdom and Australia. In 1997, he and his wife, Cathy Duplantis, founded Covenant Church, a local outreach of JDM on the International Headquarters property in Destrehan, Louisiana. The JDM official website states: "Jesse Duplantis Ministries is an evangelistic ministry dedicated to reaching people and changing lives with the Gospel of Jesus Christ. Our vision is world evangelism and our desire is to see God bless everyone in every way." Duplantis' books have been translated into thirteen languages, including Braille, and are distributed worldwide. Duplantis appears on the internet via webcasts, a variety of Christian television stations such as the Trinity Broadcasting Network, Daystar, and LeSEA, in addition to secular networks inclusive of the ABC, NBC and CBS. Duplantis is considered a preacher of the prosperity gospel.
In recognition of his "many years of effectively sharing God's message of salvation through Jesus Christ to the world," Jesse Duplantis was awarded an honorary Doctorate of Divinity degree from Oral Roberts University in 1999.
In early 2006, Duplantis was invited to become the first Louisiana Director of Christians United For Israel (CUFI). He states, "CUFI has asked me to be the Louisiana Director, and it's an offer I've accepted. I believe that Christians like us should stand for Israel and the Jewish people." A diverse group of Christian leaders met in San Antonio February 7–8, 2006 to form the organization, which is chaired by John Hagee.
In 2016, Duplantis and fellow televangelist Kenneth Copeland defended their use of private jets with the claim that commercial planes were full of "demons".
In May 2018, national news media outlets accused Duplantis of asking his followers to donate money to him so that he could buy a new $54 million private jet, the Dassault Falcon 7X. Duplantis said that his organization, Jesse Duplantis Ministries, had already paid for three private jets by 2006, and that he had been using them by "just burning them up for the Lord Jesus Christ." Duplantis defended his choice by saying: "I really believe that if Jesus was physically on the earth today he wouldn't be riding a donkey. Think about that for a minute. He'd be in an airplane preaching the gospel all over the world." In response to a wave of criticism, Duplantis stated on his ministry website, "I'm not asking you to pay for my plane, I'm asking you to pray for my plane."