Fastest: TGV from Gare d'Austerlitz to Gare de Blois, ~1h25m; Intercités ~2h. Several trains/hour. Tickets from €25 one-way; group discounts available.
~2h30m from Gare de Bercy, Gare de Massy-Palaiseau, or CDG Airport to Gare Routière de Blois. Tickets from €15.
~2h via A10 to Orléans then A71 to Blois. Well-marked route.
Tips: Book ahead, fill tank, use GPS, park near station or city center. Explore Château de Blois, Cathédrale Saint-Louis, Musée d'Art et d'Histoire.