New Orleans, which was ravaged by Hurricane Katrina in 2005, leaving hundreds dead, and other cities on the US Gulf coast were under a hurricane warning.
Louisiana, the state home to New Orleans, said President Donald Trump had quickly approved the release of federal aid to help mitigate the impact of the storm.
With the storm's top winds swirling at 129 kilometers (80 miles) per hour some 240 miles northwest of the western tip of Cuba, the US National Hurricane Center (NHC) warned that in the United States, "the combination of a dangerous storm surge and the tide will cause normally dry areas near the coast to be flooded by rising waters moving inland from the shoreline."
The water was expected to peak at up to 2.5 meters (eight feet) above ground in some areas.
Luis Felipe Puente, national coordinator of Civil Protection, recommended "avoiding aquatic, touristic and recreational activities" in Quintana Roo.
After moving across the Gulf of Mexico, the storm was set to make landfall along the central US Gulf Coast late Saturday, the NHC said.
Authorities canceled school in seven Mexican coastal towns and declared an orange alert for the northern half of Quintana Roo state.
Swells expected to affect northwestern Caribbean land over the weekend "are likely to cause life-threatening surf and rip current conditions," according to US forecasters.
New Orleans issued a mandatory curfew for Saturday from 6:00 pm (2300 GMT), and mandatory and voluntary evacuation orders were issued for certain low-lying areas.
"Our greatest threat... is not necessarily rain, but strong winds and storm surge," said New Orleans Mayor Mitch Landrieu.
Unlike Hurricane Harvey, which dumped record amounts of rain while hovering over neighboring Texas for a week, fast-moving Nate was expected to quickly pass along a northerly path.
Louisiana Governor John Bel Edwards warned that while Nate was forecast to be a weak hurricane, it could still cause unexpected damage.
"Anyone in low-lying areas... we are urging them to prepare now," he said.
In the neighboring state of Mississippi, lines formed at gas stations in areas within the potential path of the storm.
Some offshore oil and gas rigs in the Gulf of Mexico were evacuated ahead of the storm's advance.
Nate was still wreaking havoc in Central America, where heavy rains continued causing floods.
Authorities in El Salvador, Guatemala and Honduras have declared a maximum or red alert.
On Thursday, intense rains forced thousands from their homes, uprooted trees, knocked out bridges and turned roads into rivers across a swath of Central America.
"We were drowning. Thank God (emergency workers) helped us. The river swelled so much it swept away our house, our pigs, our chickens -- it swept away everything," said Bonavide Velazquez, 60, who was evacuated from her home in southern Nicaragua.
Nicaragua bore 13 of the deaths, according to Vice President Rosario Murillo.
In Costa Rica, where a national emergency was declared, 10 people died, including a three-year-old girl, after they were hit by falling trees and mudslides. An alert was issued for people to be wary of crocodiles that might be roaming after rivers and estuaries flooded.
Three other people were killed in Honduras, and two in El Salvador.
More than 30 people are listed as missing across the region.
The United States is recovering from two major hurricanes: Harvey, which tore through Texas in August, and Irma in September.
Another powerful storm, Hurricane Maria, ripped through the Caribbean in late September, devastating several islands, including Dominica and Puerto Rico.
Central America, the Caribbean, Mexico and the southern United States suffer an Atlantic hurricane season every year that runs from June to November.
But 2017 is already one of the worst years on record.
(This story has not been edited by NDTV staff and is auto-generated from a syndicated feed.)