The Piper PA-28 landed at Exit 33 / Route 109 in East Farmingdale around 11:40 a.m.
The flight took off from Republic Airport just before 10 a.m. and was attempting to return to the airport after the pilot reported engine failure.
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The plane, carrying two occupants, could be seen flying low over Suffolk County until it made an emergency crash-landing on the highway.
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Both of the occupants in the plane are being treated at local hospitals for minor injuries.
A stretch of the road was shut down to give crews an opportunity to remove the plane, which snarled traffic for the afternoon.
The Southern State, which is on the South Shore, is one of the main highways on Long Island.
New York State Police, the FAA and the NTSB will all investigate.
State Police are asking for any witnesses or anyone with information to call (631) 756-3300.
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