In an Instagram post, Harris said that he and his wife, Shannon, had experienced some "significant changes".
The couple, who married in 1998, came to the decision to separate "out of sincere love for one another", he said, adding that they wanted to create a "generous and supportive future for each other" and their three children going forward.
"We're writing to share the news that we are separating and will continue our life together as friends. In recent years, some significant changes have taken place in both of us," he wrote.
"It is with sincere love for one another and understanding of our unique story as a couple that we are moving forward with this decision.
"We hope to create a generous and supportive future for each other and for our three amazing children in the years ahead.
"Thank you for your understanding and for respecting our privacy during a difficult time."
The post has split opinion on Instagram, with some people criticising them for the decision, while others offered their prayers and words of support.
Harris is the former pastor of Covenant Life and is best known for "I Kissed Dating Goodbye", a book about purity and courtship that became a bestseller following its release in 1997.
The book is written primarily to young Christians and its central argument is that dating is something to be avoided.
It strongly encourages purity and abstinence before marriage but controversially argues that even non-romantic relationships between Christians of the opposite sex can be damaging and that the more a person dates, the more they are giving away a part of their heart.
While the ideas quickly caught on at the height of the purity movement in the 90s, they later came under increasing scrutiny, with some Christians arguing that they had done more harm than good.
In 2015, Harris appeared to agree with these concerns, announcing that his own thinking on Christian dating and courtship had evolved in the years since he wrote "I Kissed Dating Goodbye".
In a move that caught many Christians by surprise, he offered a sincere apology to anyone who might have been "misdirected or unhelpfully influenced" by the concepts and ideas in his book.
"While I stand by my book's call to sincerely love others, my thinking has changed significantly in the past twenty years. I no longer agree with its central idea that dating should be avoided. I now think dating can be a healthy part of a person developing relationally and learning the qualities that matter most in a partner," he said in a statement.
"There are other weaknesses too: in an effort to set a high standard, the book emphasized practices (not dating, not kissing before marriage) and concepts (giving your heart away) that are not in the Bible. In trying to warn people of the potential pitfalls of dating, it instilled fear for some—fear of making mistakes or having their heart broken.
"The book also gave some the impression that a certain methodology of relationships would deliver a happy ever-after ending—a great marriage, a great sex life—even though this is not promised by scripture," he continued.
"To those who read my book and were misdirected or unhelpfully influenced by it, I am sincerely sorry. I never intended to hurt you. I know this apology doesn't change anything for you and it's coming too late, but I want you to hear that I regret any way that my ideas restricted you, hurt you, or gave you a less-than-biblical view of yourself, your sexuality, your relationships, and God."