Miami-Dade Mayor Carlos Gimenez issued an evacuation order for residents living in mobile parks and low-lying areas Saturday afternoon.
MORE: Residents brace for Isaac, Pasco issues state of emergency
He said three shelters will open in Miami-Dade County.
Tropical storm force winds from Isaac could begin in South Florida as early as Sunday morning.
MORE: Florida Keys ask tourists to leave as Isaac strengthens
He urged residents to begin putting up their shutters, gather supplies and fill up their cars with gas.
"You should begin putting up your shutters now. Even tropical storm winds can cause damage so you shouldn't wait until the last moment to protect your home," he said.
Miami International Airport will remain open but six flights had been cancelled on Saturday. The Fort Lauderdale-Hollywood International Airport was also to remain open, but 10 flights were cancelled. Click here for status of flights there.
Meanwhile, public schools in Miami-Dade and Broward County were canceled Monday.
"Things have changed in the last less than 24 hours, we thought we were going to be in a much better situation, things have shifted to the right and to the east, and we may have a hurricane instead of just a tropical storm," Gimenez said.
He said residents should have food and water for three days, secure outside furniture and stay alert to the latest storm developments.
Broward County will also open homeless shelters and buses were picking up people at designateed locations. They are the Broward Outreach Center at 2056 Scott Street in Hollywood, Pompano Beach City Hall on Atlantic Boulevard and First Avenue and at the Salvation Army Lodge at 1445 West Broward Boulevard in Fort Lauderdale.
The National Weather Service and the National Hurricane Center meanwhile, are busy forecasting Isaac and encouraging South Florida residents to take preparations ahead of the storm.
Dade and Broward could have several inches of rain and tropical storm force winds, while the Keys could experience hurricane force winds, they said.
"Today is really the day when we need to start doing our preparations because by tomorrow, especially for mainland South Florida, at least by late tomorrow morning, we could already be starting to experience the first tropical storm winds," Robert Molleda of the National Weather Service told NBC 6. "And then as the day goes on Sunday, those winds will be become more steady and then by night, those winds will probably be at their highest point."
The agencies also say to keep in mind that the forecast track could still change slightly depending on land interaction with Cuba, so they urge residents to not let their guard down.
"It's a pretty large storm," Molleda said. "That tropical force wind field, even if the center passes over the lower Keys, Miami-Dade and Broward County will likely see some tropical force storm winds, probably for most of the day on Sunday."
As of 2 p.m., Isaac was located about 40 miles north of Guantanamo, Cuba and 325 miles south-southwest of Nassau. The center of Isaac was nearing the north coast of Eastern Cuba. Isaac had maximum sustained winds at 60 mph and was moving northwest at 17 mph.
Zoo Miami was closed Saturday due to bad weather brought by Isaac. Jungle Island is closing Saturday at noon and all day Sunday. Miami Seaquarium will be closed at 2 p.m. Saturday and all day Sunday.