The US Supreme Court is deciding whether to legalise same-sex marriage across America which Mr Graham has described as "the most historic and far-reaching judgment of the 21st century".
The president of Samaritan's Purse and of the Billy Graham Evangelistic Association posted on Facebook that Americans should "pray fervently for the wisdom and counsel of God to work its way into their hearts and minds of those making this momentous decision."
He added that: "If our nation's highest court decrees same sex marriage as the law of the land, the consequences will be great.
"It sets the stage for persecution of believers committed to living by the truth of God's Holy Word."
Commenting on a story by the Washington Post about Barronelle Stutzman, a florist, who refused to prepare flowers for her gay friend's wedding he said: "I commend Barronelle Stutzman for living by the biblical principles of her Christian faith, no matter the cost."
He stressed this example showed that the principles of gay marriage will affect "each and every one of us" and that there will be "a storm of persecution against all people who follow God and His standards if this passes."
A decision on the issue is expected later in the year.