I live in Canada, the part closest to Florida, and, during our drive to WDW down I-75, I drove for almost 21 hours our first day (it would have been about 17 hours, but we got stuck in a horrible traffic jam after a rockslide just over the border in Tennessee). TBH, I really didn't start to feel tired until the last hour of our trip, but the next day, I was physically and mentally drained. Having said that, the last 2 drives to Florida, my wife and I shared the driving, and I felt much better (plus, I was able to actually take in some of the scenery in the mountains of Tennessee).