Isaac tracked between Guadeloupe and Dominica late on August 22, and then turned towards the west-northwest and entered a region favorable for intensification; it passed over Haiti and Cuba at strong tropical storm strength.

The system gradually weakened once inland, but still produced a widespread tornado outbreak across the middle of the country before dissipating into an open low early on September 1.

Tropical storm-force sustained winds, with gusts well over hurricane strength, knocked out power to hundreds of thousands, and heavy rain led to flooding.

As an extratropical cyclone, Isaac produced torrential rains across Arkansas, flooding numerous streets and homes, and damaging many crops across the region.

[7] Late on August 21, a Hurricane Hunters mission observed flight-level winds of 51 mph (82 km/h), and on this basis the NHC upgraded the depression to Tropical Storm Isaac.

[21] After further intensification, Isaac made landfall at 2345 UTC (6:45 p.m. CDT) on August 28, just southwest of the mouth of the Mississippi River with winds of 80 mph (130 km/h).

[29] The depression continued generally northeastward over Arkansas and Missouri before transitioning into an extratropical cyclone on September 1 as it interacted with an upper-level trough.

On September 3, the mid-level circulation of the storm split into two parts, with one portion continuing southward into the Gulf of Mexico and the other eastward over Ohio.

[30] By the end of the day, tropical storm warnings were in place for was issued for Anguilla, Antigua, Barbuda, the British Virgin Islands, Culebra, Dominica, Guadeloupe, Desirade, Les Saintes, Marie Galante, Martinique, Montserrat, Nevis, Puerto Rico, Saba, St. Eustatius, St. Maarten, St. Martin, St. Kitts, United States Virgin Islands, and Vieques.

[39][40] Oil production in the Gulf of Mexico was down by 24% percent and gas off by 8%, as several major companies (including BP and Shell) evacuated their installations in the east part of the basin.

According to the Republican National Convention spokesman James Davis, officials had been coordinating with the United States Secret Service, should the 50,000 politicians, delegates, and reporters require evacuation.

In Walton County, special needs and general shelters were opened to the public, and all schools and government offices were to be shut down throughout the duration of the storm.

President Michel Martelly canceled his trip to Japan to coordinate emergency response efforts and visit residents with Prime Minister Laurent Lamothe.

The resultant flooding left entire neighborhoods isolated and caused damage to homes, businesses, and roads in Palm Beach County.

Winds were stronger in Miami-Dade County, reaching 60 mph (97 km/h) at the Atlantic Oceanographic and Meteorological Laboratory (AOML) headquarters in Virginia Key.

[50] Heavy rainfall fell in portions of Broward County, peaking at 11.21 inches (285 mm) at the intersection of State Road 997 and Interstate 75 near Weston.

Wind gusts were estimated to have reached 60 mph (97 km/h) in Tequesta, where the shutters were ripped from a life guard stand and also moved the structure about 3 feet (0.91 m) from its original location.

[102] In Palm Beach County, the outer bands dropped significant amounts of rainfall, with radar estimates as high as 20 inches (510 mm) in some areas.

[104] The entrance to the gated community of Lawrence Grove in Boynton Beach was flooded by about 1 foot (300 mm) of water and passable only by large pickup trucks.

Streets were littered with small branches and palm fronds in Boca Raton, while low-lying roads and swales were flooded with several inches of water.

[80] Due to its weaker and further westward track than initially anticipated, impact in Hillsborough County and the city of Tampa was minimal during the Republican National Convention.

The depth of inundation along 7th Avenue in Panama City ranged from a few inches to about one foot, while other roads in Lynn Haven and West Bay were also flooded.

[116] At the coast, the system's large size generated a strong storm surge that caused extensive damage to low-lying areas of the state.

Areas of Plaquemines Parish were estimated to have been submerged under as much as 17 ft (5.2 m) of water, based on pressure sensors from the United States Geological Survey.

The rising water levels later overtopped the levee height, causing it to overflow and inundate primarily uninhabited areas between Braithwaite and Belair.

[63] There are about 2,132 evacuees housed in 31 shelters across the state and about 4,000 homes were without power as of 5:30 a.m. CT.[131] A man was crushed in the cab of his tow truck in Picayune, Mississippi after a tree fell on it, while he was on a call to assist a stranded motorist.

[135] Coastal flooding was reported in several towns in Mobile and Baldwin Counties including Bayou la Batre,[136] Gulf Shores and Orange Beach.

The worst river flooding impacts were felt in Brooklyn, Arkansas, where the nearby Black Creek caused damage to 15 homes near its banks after overflowing.

A Florida state fund known as Neighbors to the Rescue – with the purpose of distributing money to help recovery efforts for victims of Isaac – was activated by the governor.

[140] The appeal was accepted, and on October 18, 2012, President Obama issued a disaster declaration for Bay, Collier, Escambia, Franklin, Gulf, Martin, Monroe, Okaloosa, Palm Beach, St. Lucie, and Santa Rosa counties.