The state highway runs 23.17 mi (37.29 km) from Tilghman Island east to Washington Street in Easton.

The state highway passes through the historic town of Saint Michaels, home of the Chesapeake Bay Maritime Museum, and enters Tilghman Island by passing over Knapps Narrows on the busiest bascule drawbridge in the United States.

The state highway was constructed between Easton and Claiborne, the terminus of a ferry to Annapolis, in the late 1910s and early 1920s, and was originally designated MD 17.

The state highway was extended north to MD 404 in Matapeake on Kent Island when the western terminus of the ferry from Claiborne was moved to Romancoke in the late 1930s.

The state highway passes the northern terminus of MD 579 (Bozman Neavitt Road) and around the head of Broad Creek before curving south and passing through the town of Saint Michaels and its namesake historic district.

MD 33 is known as Talbot Street within the town, where the highway passes the entrance to the Chesapeake Bay Maritime Museum, marked by the previous drawbridge over Knapps Narrows.

The state highway curves to the southeast within the town and passes southwest of St. Michaels Middle/High School before it continues straight out of town through a mix of farmland and forests until the hamlet of Newcomb, where MD 329 (Royal Oak Road) splits to the south toward Royal Oak and Bellevue, the latter location being where the seasonal Oxford–Bellevue Ferry crosses the Tred Avon River to the town of Oxford, while MD 33 curves east to cross Oak Creek along the shore of the Miles River.

[1][2] MD 33 is a part of the National Highway System as a principal arterial from the west town limit of Easton to Washington Street.

[7] The first sections of modern MD 33 constructed by the State Roads Commission were between Saint Michaels and Claiborne, which became the terminus of the Claiborne–Annapolis Ferry in 1919.

[3] The 1934 drawbridge was transferred to the entrance of the Chesapeake Bay Maritime Museum in Saint Michaels.