"It's a very painful and difficult time of spiritual discernment for all of us," Henderson said, although he declined to say why he is leaving. He has led the 2,300-member congregation since September 2007.
Henderson, 56, said a congregational meeting has been set for next Sunday, at which time the congregation will vote on whether to petition the Presbytery - which oversees the governing body of the church - to dissolve Henderson's contract as pastor.
A nominating committee will then be selected to search for a new pastor.
"This is a wonderful congregation, and I wish the very best for the congregation, its lay leaders and its staff," said Henderson, who grew up in North Carolina. He does not have plans for his immediate future, he said.
First Presbyterian sits at 189 Church St. near the Marietta Square. Its last senior pastor, David Jones, left in 2005. He succeeded Jim Speed, who had led the church for 25 years.
Georgia State Supreme Court Justice Harris Hines, clerk of "session," the governing body of the church, alluded to managerial style issues between Henderson and the other church ministers.
"I'm sure people will be sad to see him go. Everybody wishes the best for him, and the best for our church," Hines said. "He's a good man, he's a decent man, and we wish him continued success in his ministry."