The Grand Central Parkway begins at the Robert F. Kennedy Bridge overlapped with I-278 in the Astoria section of Queens.

The Grand Central then proceeds south, crossing under the Long Island Rail Road's Port Washington Branch and soon into Flushing Meadows-Corona Park.

Through the park, the parkway passes west of Arthur Ashe Stadium, the Queens Zoo and the Unisphere before entering exit 10, a cloverleaf interchange with the Long Island Expressway (I-495).

After that interchange, the parkway bends southeast through Forest Hills, passing Willow Lake and exit 12, which connects to NY 25 (Queens Boulevard) via 78th Avenue.

After the Kew Gardens Interchange, the Grand Central Parkway continues east into the Briarwood section of Queens, where exit 16 connects to Parsons Boulevard via a service road.

After crossing through the developed neighborhood of Briarwood, the parkway enters Jamaica Hills, passing south of Queens Hospital near 164th Street.

[3] At the interchange with Utopia Parkway, the Grand Central passes south of St. John's University, soon winding northeast into exit 19, which serves 188th Street in Jamaica Estates.

Exemptions were provided for smaller trucks that conform with strict regulations on the section of the Grand Central that overlapped with I-278.