It begins in the north at Leverett Circle, where it connects with Nashua Street and Monsignor O'Brien Highway.

Science Park station on the MBTA Green Line is located there.

Charles Street runs south and gives its name to the Charles/MGH station on the MBTA Red Line, connecting via the Charles Circle rotary to Cambridge Street and the Longfellow Bridge which leads to Cambridge.

From Charles Circle, the street heads further south as a one-way southbound thoroughfare, and forms the primary commercial spine of the affluent neighborhood of Beacon Hill.

As it crosses Beacon Street, the direction of one-way traffic reverts to northbound, and the street widens to form the boundary between Boston Common and the Boston Public Garden.