Just go up Route 611.
The best interstate route from Knoxville, TN, to Buffalo, NY, is to take I-75 North to I-40 East, then merge onto I-81 North. Continue on I-81 until you reach I-86 East, which will lead you toward Buffalo. This route offers a balance of efficiency and scenic views, covering approximately 600 miles.
Take the New Jersey Turnpike SOUTH to the Philadelphia area.
I-90 EAST to Buffalo.
Take U.S. 26 EAST to I-25. Follow signs. You want I-25 NORTH to the MIDWEST.Take I-25 NORTH to Buffalo.
Qew west to hamilton.continue on qew.then merge onto the 405 to Lewiston Bridge .then to I-190 N .exit at Route 33 Arrive at Buffalo,NY
The driving distance between Buffalo NY and Philadelphia PA is 381 road miles.
Philadelphia, PA (PHL) to Buffalo, NY (BUF)Shortest Flight Duration 1 hour 19 mins
A buffalo cheesesteak sandwich
Take the I-76 turnpike EAST to Philadelphia.
Too many.
377 road miles to Buffalo, NY using US-15 N.