The state highway originally passed through downtown Cambridge, ending just west of its present terminus.

The state highway heads east as a two-lane undivided road through a mix of farmland and forest, intersecting roads that serve the peninsulas split by creeks that flow into the Choptank River to the north and the Little Choptank River to the south.

Shortly after passing Horns Point Road, which leads to a golf course and the Horn Point Laboratory of the University of Maryland Center for Environmental Science, the state highway passes a few residential subdivisions and enters the city limits of Cambridge, where the highway's name changes to Washington Street.

[1][2] MD 343 is a part of the National Highway System as a principal arterial within the city of Cambridge.

[1][3] MD 343 was paved from the western city limit of Cambridge to Horns Point Road by 1921.

[4] The state highway was paved within Cambridge and extended west to Town Point Road by 1923.