The Florida Highway Patrol said the crashes occurred around 5 a.m. at the 293 mile post in Dade City, near the Hernando County line and between State Roads 50 and 52.
One man was airlifted to Bayonet Point Hospital with serious injuries, the FHP said.
Southbound traffic is being diverted onto State Road 50 at exit 301, the FHP said.
The FHP estimates crews will continue to clear the road for the next 1-2 hours.
Motorists should use U.S. 301 as an alternate.