From Williamsburg:

Take the Colonial Parkway to Yorktown.  Take the left exit marked "Yorktown Victory Center." At the end of the exit,  turn left onto Water Street at the Victory Center entrance.  Follow Water Street for about 1/4 mile.  The Watermen's Museum is on the left.   

From Richmond:

Take I-64 east to exit 250B (Route 105, Fort Eustis Blvd.) to Yorktown.  The exit ramp will lead you to a right turn onto Fort Eustis Blvd.  Follow this road until it ends at Route 17.  Turn left onto Route 17.  At the last exit before the Coleman Bridge, turn left onto Mathews Street.  (This exit is literally at the foot of the bridge.)  Follow Matthews Street about one block to the end where it meets Water Street.  Turn right onto Water Street.  The Museum is on the left.

From the Lower Peninsula:

Take I-64 west to Route 17 north, aka J. Clyde Morris Blvd.  Follow Route 17 towards Yorktown.  At the last exit before the Coleman Bridge, turn left onto Mathews Street.  (This exit is literally at the foot of the Bridge.)  Follow Matthews Street about one block to the end where it meets Water Street.  Turn right onto Water Street.  The Museum is on the left.

From Gloucester:

Take the Coleman Bridge towards the Peninsula.  Immediately after the bridge, take the first right turn onto Mathews Street. Follow it about one block to where it meets Water Street.  Turn right onto Water Street.  The Museum is on the left.  

Parking

Parking is across the street from the Museum or adjacent to the Museum on either side.