"Every indication is that America will go down the drain if in fact she is elected," he told FOX Business Network's Neil Cavuto in a recent interview.
"When I listen to Hillary Clinton and I listen to the [economists] who never in their life ever hired a human being or trained a human being, I say, I don't know the world that they belong in. I know that when you have high taxes that you kill off jobs. Killing off jobs means hurting America. It means hurting the economic wealth of America - and that's not good for anybody."
He accused the Clintons of being a "corrupt family" and urged Republicans to vote for Donald Trump even if they don't like him.
"All of the Republicans out there, I say the same thing… [If you're] going to stay neutral, you might as well vote for [Hillary Clinton] because your lack of vote for Donald means she's going to get elected anyway," he said. "You may not like him, but you [have to] vote for him because he's going to save this country."
Marcus, 87, co-founded Home Depot in 1978 and he was the company's first CEO. He served as chairman of Home Depot's board until retiring in 2002.
Marcus made the remarks after another prominent businessman, Starbucks CEO Howard Schultz, last week endorsed Hillary Clinton for president.
"Hopefully Hillary Clinton will be elected president," Schultz told CNN's Poppy Harlow in a Facebook Live interview.
Schultz has long been outspoken about his political and social views, but last week was the first time he has weighed in on the 2016 presidential race.