Most of NY 43 is a two-lane highway that passes through a mixture of rural and residential areas; however, its westernmost mile is a four-lane freeway.

Initially, the portion of modern NY 43 east of Averill Park was designated as part of New York State Route 7 in 1924.

NY 43 begins at an interchange with I-90 (exit 8) in the town of North Greenbush in western Rensselaer County.

The route heads northeastward as a four-lane freeway through a small forest separating NY 43 from a pair of residential neighborhoods.

NY 43 narrows to two lanes roughly 0.25 miles (0.40 km) east of US 4 and continues eastward through a densely populated area of North Greenbush.

[4] East of Lape Road (County Route 66 or CR 66), the amount of development along NY 43 begins to decline and give way to small, open fields located amongst forested areas.

However, as NY 43 enters the town of Sand Lake, the number of homes and businesses on the highway rises once more.

NY 43 serves as the main commercial strip through the hamlet, which is the largest location on the route since Averill Park.

[15][16] NY 43 was truncated on its western end to the junction of 3rd Avenue and Broadway in downtown Rensselaer in the early 1970s, eliminating the overlap with US 9 and US 20 through Albany.

The realignment eliminated the overlap with US 4 and also took NY 43 outside of the Rensselaer city limits for the first time since being extended across the Hudson River in 1930.