The storm -- the strongest to threaten the US coast in more than a decade -- is poised to shake the campaigns with just 33 days remaining before the election.
Safety is the biggest concern as Matthew approaches Florida and later takes aim at North Carolina, another crucial swing state. But the hurricane is also threatening Clinton and Trump efforts to mobilize voters. And the potential of displaced residents could challenge pollsters and scramble turnout.
The Clinton campaign had asked Florida officials to extend the state's October 11 voter registration deadline to account for the storm. But Florida Gov. Rick Scott told reporters Thursday he doesn't "intend to make changes," explaining that "people have had time to register."
Steve Schale, a Democratic strategist in Florida who ran President Barack Obama's 2008 race and several other campaigns in the state, said the get-out-the-vote activities are designed to build day-by-day and "ramp up to a goal."
Those plans, he said, will be at least temporarily interrupted.
"Obviously, any day off the campaign is not a good one," Schale told CNN Thursday.
The storm is essentially freezing the 2016 campaign in place as candidates on both sides avoid Florida for the next few days.
"We're very mindful of the fact that a visit at the wrong time, when people are really focused on keeping themselves safe, would be a real distraction," Democratic vice presidential nominee Tim Kaine said Thursday on CNN's "New Day."
The storm is forcing the campaigns to scramble across Florida -- even outside the state's evacuation zone. Orlando, and the sprawling surrounding area, is home to many of the state's Puerto Rican voters who are top targets of the Clinton campaign. Field offices were closed and campaign workers were evacuating, aides said Thursday.
Republican National Committee political director Chris Carr said the party suspended its voter contacts in Florida Wednesday at noon "so that our staff can make plans in preparation for the storm."
Both campaigns face risks in shuttering significant portions of their voter turnout operations temporarily: Clinton's operation has vast organizational muscle -- and therefore more to lose. Trump has been playing catch-up in swing states, and could find himself running even shorter on time.
"You do worry about it, you fret about it," said Brett Doster, a Tallahasee-based GOP strategist who aided George W. Bush's 2004 re-election campaign in Florida.
"And if you're a good state executive director," Doster said, "what you're probably telling your employees and volunteers to do right now is to stay safe -- and then after the storm's over, put on a Trump or Clinton T-shirt and go help people out, start handing out water. That's about all you can do."
Doster said hurricanes cause a delay of about a week to 10 days, when "recovery becomes way more important than a partisan label."
"That will sort of set a time-out in the game, so to speak," he said. "But it doesn't prevent people from doing things to get ready for the partisan games again once that period passes, and my guess is that both campaigns right now are going to be thinking about what go time looks like, and they will pick up immediately afterward."
Already, Clinton's campaign ran into criticism for a move that gave the appearance she was capitalizing on a deadly storm. Earlier in the week, the campaign spent $63,000 on advertisements to air on The Weather Channel -- which would have aired during coverage of the hurricane, while the station's viewership swelled.
On Thursday, Clinton's campaign -- facing backlash from Republicans including former Florida Gov. Jeb Bush spokeswoman Kristy Campbell -- delayed that buy until after the hurricane
Test for governors
Matthew isn't just a test for presidential candidates.
Governors like Scott and South Carolina's Nikki Haley will be judged for their response.
In North Carolina, incumbent Republican Gov. Pat McCrory is struggling against Democratic challenger Rory Cooper in another race that could hinge on McCrory's handling of disaster efforts.
Trump, meanwhile, has personal properties at stake in Florida. His prized Mar-a-Lago estate in Palm Beach and his golf club in Jupiter could face the storm's fury.
A Trump aide said the Republican nominee "spoke to his employees yesterday to ensure they were being safe and following instructions from local officials. The club is not open for the season yet."
Trump on Thursday offered his thoughts and prayers to "everyone in the path of Hurricane Matthew" and warned residents to heed authorities' calls for evacuations.
"Nothing is more important than the safety of your family," Trump said in a statement. Trump later told a town hall audience in New Hampshire that he had spoken with Scott.
On CNN's "New Day," Trump's running mate, Mike Pence, said he would "just encourage people not only to keep the people in Florida, and up the Eastern seaboard in their prayers, but also to be supportive of organizations like the Red Cross that are going to be tested in the days ahead as they come alongside families."
Natural disasters have intervened repeatedly in recent presidential contests -- starting in 1992, when Hurricane Andrew slammed into Florida as President George H.W. Bush squared off in a general election battle with then-Arkansas Gov. Bill Clinton.
After three days of waiting for federal relief, Kate Hale, who was Dade County's emergency manager, famously stood in front of TV cameras and asked: "Where's the cavalry?"
"There was a sense that George H.W. Bush wasn't watching his backyard -- he was too busy with international affairs," said Tevi Troy, a former George W. Bush White House aide and historian who wrote the book "Shall We Wake the President? Two Centuries of Disaster Management from the Oval Office."
Past political storms
Eight years later, his son -- then a Texas governor who'd learned from his father's failures in handling disasters like fires in 1998 -- forced Al Gore into a major error. Gore, who was then vice president, claimed in a debate that he'd accompanied Federal Emergency Management Agency Director James Lee Witt on a tour of the fire-damaged lands in Texas. Gore had not, and Bush's team successfully labeled him a serial exaggerator for it.
But Bush's second term was ultimately undone by Hurricane Katrina, with federal help again slow to arrive and the President's helicopter tour of the flooded New Orleans making him appear detached.
A natural disaster again intervened in election season in 2012, when Hurricane Sandy struck the East Coast of the United States.
The storm stunted Mitt Romney's ability to score political points against Obama in the final weeks of the race. It sidelined New Jersey Gov. Chris Christie, a prominent Romney surrogate who was suddenly touring storm damage alongside Obama. And it thrust Obama into a leading role, demonstrating the advantage of incumbency.
Trump himself weighed in on Sandy in 2012, calling it a boon to Obama's re-election chances because of his ability to dole out federal aid.
"Hurricane is good luck for Obama again- he will buy the election by handing out billions of dollars," he tweeted on October 30, just days before the election.
Trump's own reaction to a natural disaster has already helped him once in the 2016 race: He toured Louisiana in the wake of floods there this summer, revealing a compassionate side of the bombastic billionaire.
Though 24-hour cable news has changed the importance of presidential candidates' actions, natural disasters have challenged presidents and candidates through the United States' history, Troy said.
In the country's early days -- before the advent of mass communication -- presidents did little to address disasters in part because they had no way to learn about them in real time. It took James Madison six weeks, for example, to learn that a massive earthquake had struck Missouri.
Then, there were questions about the president's role. In 1889, when more than 2,200 people were killed when a dam broke in Pennsylvania, President Benjamin Harrison sent a personal check to the victims.