It flows south for 15 miles (24 km)[2] through eastern Connecticut from the junction of the Yantic River and Shetucket River at Norwich, Connecticut, to New London and Groton, Connecticut, which flank its mouth at Long Island Sound.

[5] The United States Coast Guard Academy, Connecticut College, a U.S. Navy submarine base, and the Electric Boat submarine shipyard are located on the river at New London and Groton.

USS Nautilus was launched into the river on January 21, 1954 from Electric Boat, becoming the world's first nuclear-powered submarine.

[6] In addition to the submarine bases, a US Navy Magnetic Silencing Facility is also installed within the mouth of the river.

New London's Sailfest is an annual event which includes OpSail, a gathering of large sailing vessels including the Coast Guard training ship USCGC Eagle.