Using radio transmitters to trace male pythons, the Big Cypress National Preserve hunters found the 63.5kg reptile last week.
"The team not only removes the invasive snakes, but collects data for research, develop new removal tools, and learn how the pythons are using the Preserve".
A picture of the female python, where she was being held by a team of four, was shared on the official Facebook page of the national preserve.
In December 2017, snake hunter Jason Leon caught a 17-foot female Burmese python at Big Cypress that set a record.
"All of the python work at Big Cypress is focused on controlling this invasive species, which poses significant threats to native wildlife", the group said on its Facebook post. Some pythons also may have escaped from a breeding site destroyed during Hurricane Andrew in 1992.
"She is the largest python ever removed and she was caught because of research and a new approach to finding pythons", said officials in the Big Cypress National Preserve, the area in which the snake was captured.
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The Burmese python is native to Southeast Asia and was introduced to Florida in the 1990s, when people released their overgrown pets into the wild.
Mash and cotton rabbits, as well as foxes in the area, have effectively disappeared.
The snakes have no natural predators in Florida and the United States Geological Survey (USGS) says they have contributed to "drastic declines" of midsized mammals.
Researchers in the park track down breeding females by fitting male pythons with radio transmitters.
Tens of thousands of Burmese pythons are now estimated to be living in Florida's Everglades.
Other efforts to remove pythons have proved less successful.