EXCLUSIVE: GOP Sen. John Thune of South Dakota says he's stepping up his efforts on the campaign trail this year because "this is our golden opportunity" to win back the Senate majority.

"It’s kind of really a make-or-break moment for Republicans in the Senate. If we don’t get it done this time, the next two cycles aren’t great for us," Thune said in an exclusive national interview with Fox News. 

Thune, who as Senate minority whip is the No. 2 GOP lawmaker in the chamber, emphasized that "we’ve got to maximize the opportunity we have this time around to get north of 50," adding that "it would be great to get well north of 50."

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Democrats, as they try to maintain or extend their fragile 51-49 majority in the Senate, are playing plenty of defense as they defend 23 of the 34 seats up for grabs in November.

One of those seats is in West Virginia, a deep red state that former President Trump carried by nearly 40 points in 2020. With moderate Democrat-turned-independent Sen. Joe Manchin, a former governor, not seeking re-election, flipping the seat is nearly a sure thing for the GOP.

Republicans are also aiming to flip seats in Ohio and Montana, two states Trump comfortably carried four years ago. And five more Democrat-held seats up for grabs this year are in crucial general-election battleground states.

"We’re hoping we’re going to have the White House, that Trump will be successful, and the House, and if we can get the Senate, we’ll be in a position to do some things," Thune emphasized.

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Thune says he's doing "everything we can" to help fundraise and campaign on behalf of Republican Senate nominees challenging incumbent Democrats "to get as many of these folks across the finish line as possible."

The senator — who is one of two top contenders to succeed longtime Senate GOP leader Mitch McConnell, who's stepping down from his leadership post at the end of the year — was interviewed ahead of a two-day campaign swing earlier this week in Pennsylvania with GOP Senate nominee Dave McCormick.

"I’ve been out with a lot of the candidates," he noted. 

Thune said he made stops earlier this summer on the campaign trail in Arizona, Michigan and Ohio, and he attended six fundraising events in the nation's capital last week for GOP Senate candidates before heading to Minnesota on Thursday to headline another finance event for Eric Hovde, the Republican Senate nominee in neighboring Wisconsin.

And he said that he'll be heading to Nevada and Utah later this month. 

"Doing whatever we can to help the team, and a lot of that is just getting money in the bank so they can get their message out," he said.

As is tradition in presidential election years, the battle at the top of the ticket can influence Senate races one notch down the ballot.

Asked how the replacement of President Biden with Vice President Kamala Harris at the top of the Democrats' ticket impacts the Senate races, Thune said that "there’s no question it’s a new race, and our Senate candidates have to do the best they can to benefit from what happens at the top of the ticket."

But he also emphasized, "I still think the issue set is the same, and I think it’s going to be very hard for [Harris] to try and distance herself from the border and the inflationary spiral that’s been created by their policies… I think those issues are going to weigh heavily on voters' minds. So if it's about the issues, I think we are really well positioned to win and that should help down-ballot, too."

Thune highlighted that GOP Senate candidates need "to run their own campaigns and define their opponents and define themselves in a way that creates a contrast. I’ve always maintained that elections are about differences, and the differences couldn’t be more stark between the two parties… I think our candidates have to capitalize on that."

At the top of the ticket, Trump has increasingly attacked and insulted Harris over the past two weeks.

But Thune is cautioning Senate candidates not to stray from the issues and "don't take the bait" from the presidential race.

Republicans wasted a perfect opportunity in 2022 to win back the Senate majority they lost in the 2020 elections. But Thune emphasized that "our side is doing a lot better job targeting voters this time around and making sure that we’re turning out and getting people to the polls way better than we did two years ago."

As for his own race against longtime Sen. John Cornyn of Texas — the previous Senate GOP whip — to succeed McConnell, Thune said he's "been sitting down and meeting with all of our incumbent senators about the leadership position, and also being out on the campaign trail with these candidates helps build relationships that I think will be important when that vote happens."

Thune, who has served two decades in the Senate, touted his own legislative record of accomplishment and said, "I think people are going to be looking for leadership that is able to produce results and get things done."

"I hope to be able to make that argument when the time comes," he added. "In the meantime, we’re just working on getting the majority."

Get the latest updates from the 2024 campaign trail, exclusive interviews and more at our Fox News Digital election hub.