Take the Thruway (87 North) to exit 21

After the toll plaza make a left

Get into your right lane...get onto Rt 23 West (toward Windham)

Take 23 for approximately 8 miles.  After you pass McDonalds get into your right lane.  You will pass Rt 32 North (traffic light) then the right lane will become Rt 145 North

Take Rt 145 North (through Durham)  approximately 12 miles.  You will come to a 4-way STOP with a Flashing RED light (It will say Rt 81 to your right)

Make a left.

Approx. 1 mile down the road will "V" - bear left - you are now on Rt 354

Take this road approximately 11 more miles (you will leave Albany County, enter Schoharie County, Mannorkill, East Conesville, Conesville, West Conesville) 

In Conesville the road will turn into State Rt. 990V

The Waterfall House will be on your left hand side.

 

It takes me 2 3/4 hrs from the Throgs Neck Bridge (Queens NY) to the Waterfall House (but I can't drive 55 ...or 65 - I'm pretty good at 79.5)