State Route 16 is a numbered state highway in Maine, United States. SR-16 runs from the New Hampshire state line (signed as NH-16) at Wentworth's Junction (near Lake Aziscohos) in the west to Orono at the eastern terminus. State Route 16 runs a total of 190 miles (310 km), passing mostly through rural areas, with the largest population center at its eastern terminus in Orono at I-95.

Route 16 follows a rather circuitous route between the two states, originating in Portsmouth, New Hampshire, at Interstate 95, and re-intersecting Interstate 95 some 350 miles (560 km) later in Orono.

The following highways run concurrently with State Route 16:

Within the towns connected by State Route 16, the highway also is known by various local names:

State Route 16 originally followed present-day State Route 6 from Lagrange to the Canadian border.