In the post since June 2017, he has led the response to several extreme natural disasters, including the heavily criticised operation in Puerto Rico after a devastating hurricane.
Mr Long was also involved in a row over the use of government resources.
In a statement, he said it was "time for me to go home to my family".
Mr Long, who has years of experience in emergency management, added that this had been "the opportunity of the lifetime" and that during his tenure the agency, known as Fema, had worked in more than 220 declared disasters.
Right after he took over, powerful hurricanes Harvey, Irma and Maria hit in quick succession, devastating parts of Texas, Florida and Puerto Rico, where some 3,000 people were killed and residents remained without electricity for months.
Last year, two strong hurricanes, Florence and Michael, hit the south-eastern US. Meanwhile wildfires caused a number of deaths in California.
"The president and his entire administration provided unprecedented support to the agency as we led the nation through the historic 2017 hurricane and wildfire season," he said.
A report by the Department of Homeland Security's inspector general said Mr Long would have to reimburse the government $151,000 (£117,000) related to costs of vehicles and staff involved in private trips, many of them between Washington and his home in North Carolina.
His deputy, Peter Gaynor, will serve as acting administrator.
More about: emergency