I've never had to set up a reservation, and I usually don't because I'm never sure where exactly I will be when I start to get run down. On several trips I aimed at making it to a certain city, and nearly made a motel reservation, but ended up having to stop quite a distance before hand.
However, I know a lot of people who gauge their travel for the day, and when they start getting close to the end of their days journey they begin calling motels and hotels in the next largest city ahead of them. It's worked for them.
But, again, I've always just stopped at the nearest motel 6 or super 8 when I start to feel tired, and its always worked for me.
-Brad