I have done this commute myself several times and also have a client that sometimes commutes to Framingham. It depends on what time of day. During rush hour times of 7-9am and 4-6pm it could take anywhere from one hour to one hour and forty-five minutes. The hard thing it is hard to anticipate this as the traffic is different daily. Mid day, it should take no longer than one to one hour and fifteen minutes. The most direct and fastest route, I believe, is Rt 95 (Rt 123) to the Mass Pike.
Having lived in both places I can tell you that 95 (which becomes 128) is the way to go. 495 is nowhere near Lexington unless you get off on Rte 3, which is a disaster in itself during commute times. On a traffic-free commute run it takes 40-45 minutes to get to the central Lexington vicinity (4/225). Once there is traffic or bad weather, you could take anywhere from 30 min extra to 3 hours to get to home/work. Traffic accidents on any of the highways will make you feel you are in the worst of rush hour in downtown LA. My husband has been doing the Nbpt to Burlington/Lexington commute since 1991 and now leaves Nbpt at 6:00-6:30 AM and leaves work no later than 3:00 PM for the best commute time.... more