I-95 to I-495 to I-290 to the Mass Pike (I-90) to I-84.
From here you have several choices
1. I-84 to I-81 in Scranton. Did this last year and 81 between Scranton and Harrisburg was construction and rough.
2. I-84 to US209 to I-80 to Harrisburg to pick up I-81
3. I-84 to I-684 to I-287 across the Tappan Zee and down the Garden State Parkway or stay on I-287 to I-78 to Harrisburg to pick up I-81
After that you can take I-81 to I-64 or get off 81 at Winchester VA and take US50/US17 to I-95 in Fredricksburg. Personally I like 50/17. It's scenic.
Also, get an EZpass. Well worth it.