Route 349 begins as a limited-access spur from I-95 (at Exit 87) leading to the city of Groton.

After an at-grade intersection with Meridian Street, Route 349 becomes a four-lane divided freeway.

The surface section of Route 349 from mile post 0.89 to the junction with SR 649 is also known as the "City Police Officer William J. Snyder, Sr. Memorial Highway".

The many urban intersections through Groton center led to elevated traffic congestion.

In 1985, part of SR 649 was re-designated as Route 349, and additionally included a portion of a road leading to Avery Point, resulting in the modern alignment and designation.