Main Street's western terminus is a merging with Walnut Hill Road in North Yarmouth, at which point SR 115 continues west.

There are three distinct sections of Main Street (from east to west): Lower Falls, Brickyard Hollow and Upper Village.

Between Lower Falls and Upper Village, Main Street is about 2.2 miles (3.5 km) long and sits about 90 feet (27 m) above sea level.

The annual Yarmouth Clam Festival attracts around 120,000 people (around fourteen times its population) over the course of the three-day weekend and is centered on Main Street.

The original owner of number 5, the first house on the northern side of West Main, was Captain Samuel Drinkwater in 1803.

[3] A hospital, run by Mrs Gilbert, was on the site now occupied by Coastal Manor nursing home at 20 West Main Street.

In 2009, the owner found a shingle signed by Mr. Pomeroy confirming he was the home's builder (additional marking discovered in 2020 on the house front with date May 25, 1889), John Calvin Stevens and Albert Winslow Cobb are confirmed architects via house plans on file at Yarmouth Historical Society.

He is also credited with several other projects, including the original Town Hall and schools and Main Street Baptist church.

[3] A large wooden building located at the intersection of West Main Street and Sligo Road, next to the old brick schools, served as the town hall between 1833 and 1910.

[3] 233 West Main Street is an imposing three-storey, fifteen-room Italianate mansion that was built for ship captain Reuben Merrill (1818–1875) in 1858.