There are two main routes to come into Big Bend from San Antonio. I-10 takes a northerly route to Fort Stockton. You may also take US 90 through Uvalde and Del Rio, which is a little shorter distance wise, but takes a bit longer.
There are a couple of ways to drive to Big Bend from Odessa and Midland, depending on your local destination.
There are several scenic routes through the Hill Country going from Austin to Big Bend, but fastest is to take US 290 west through Fredericksburg and Harper, which intersects with I-10 just east of Junction.