As you can imagine, there are many ways to get to Williamsburg.  I have found that generally the quickest way is to take Rt. 15 South to Frederick, then I 270 South to the Washington DC beltway (I 495).  You pick up I 95 South from the beltway toward Richmond and then take the I 295 Richmond beltway toward Virginia Beach to I 64 east.  Best case scenario going this route is a little over 4 hours (without stops).  HOWEVER, you risk more traffic around the DC beltway going this way so I would advise against it if you expect to be passing through DC during the rush hour.

The other route I prefer (at least coming from Carlisle) is to take I 81South to Winchester and pick up Rt 17 South from there to Fredericksburg.  At Fredericksburg you can then pick up I 95 South and the directions for the rest of the trip are the same as the first option above.  The drive on Rt. 17 is pleasant and scenic and generally not too busy.  Best case (from Carlisle) going this route is 4 1/2 hours (without stops).

A third alternative is a bit of a combination of the two - take Rt. 15 South the whole way to Warrenton Va, which is at the intersection of Rt. 15 and Rt. 17.  Then follow Rt. 17 South to Fredericksburg as in the second option.  I don't usually go this way because I am usually starting from Carlisle, so the second option above is better.  I think the trip down Rt 15 is pleasant but may have more stops/red lights.

Once you are on I 64 East, the simplest route to the motel is to get off at Exit 234 onto VA-199.  Continue on VA-199 to the Monticello Ave Exit/VA-321.   In 1/2 mile turn left onto News Rd, then right onto Ironbound Rd and the resort will be on your right.

The Powhatan Resort address is 1301 Ironbound Rd, Williamsburg, VA.