The prominent theologian has now changed his mind twice about his support for Republican candidate Donald Trump in the presidential race.
Writing a piece on blog site townhall.com, he said he came to the conclusion after thinking: "Voting for Clinton and her ultra liberal policies is not an option for me as an evangelical Christian.
"Therefore I am left with two options: (1) vote for Trump, or (2) vote for a third-party candidate whose hopes of winning belong to fantasy, not reality."
He had previously been one of the few senior evangelicals to publicly offer their support to Trump, before withdrawing it.
Speaking at the earlier in the month he said he was unsure how to vote in next month's election but was hoping there will be a new Republican candidate by then.
He had been commenting after a video from 2005 emerged of Donald Trump using sexist and predatory language about women.
Mr Grudem had said Trump was immoral, but now his blog said that the candidate "claims he is a changed person from who he was in 2005 and he has apologized for how he acted back then.
"There is a possibility he has really changed, and I hope it is true."
He asks "Why not vote for the candidate whose policies are best?"
He cites abortion, changes to the Supreme Court under Hillary Clinton, and religious liberties as to why he favours Trump's policies.
Wayne Grudem concludes: "The most likely result of not voting for Trump is that we will be abandoning thousands of unborn babies who will be put to death under Hillary Clinton's Supreme Court, thousands of Christians who will be excluded from their lifelong occupations because they won't affirm same-sex marriage."
Americans go to the polls on November 8th to elect either Democrat Hillary Clinton, or Republican Donald Trump.
