Facing a stiff challenge from former Democratic Ohio Gov. Ted Strickland, Portman said Republicans need to win Ohio at the top of the ticket and down the ballot. President Barack Obama won Ohio in 2008 and 2012.
"People are frustrated" with the lack of economic growth during Obama's presidency, Portman said. "Trump and Bernie Sanders are different sides of the same coin."
The delegate math is not favoring Sanders, even though he's won three out of the last four Democratic presidential primaries. On Tuesday's he's expected to win in Oregon, while Clinton hopes for victory in Kentucky.
"Trump is going to be the change agent," Portman said. "Hillary Clinton is going to be the status quo. Bernie Sanders is not going to be in the mix."
Portman feels it's more important than ever for Republicans to unite, saying it looked like last week's meeting of Trump and House Speaker Paul Ryan went well, though Ryan has not endorsed Trump.
"Paul's got to do what he's got to do. He does have some good points on some of the policy differences. I think they'll work those out," said Portman.
The senator said he has his own policy agreements and disagreements with Trump. Portman said he supports Trump's desire to crack down on China's currency manipulation, but not Trump's call in the face of terrorism concerns to temporarily ban Muslim travelers from entering the United States.
"I don't know how you'd implement that. I don't think it's right. I don't think it's constitutional to have a religious test," Portman said.