The time I done this journey it took me 7 hours (with stopping) just to get to the start of the Keys then you have another 100miles across the Key Islands to reach Key West (great journey) without stopping you could could do it 7.5 - 8.0 hours but I would stop off for the night at Key Largo the first Island and then take a slow drive along Overseas Highway 1 across the Key and just take in the sights.
as Jenny said Key Largo is the place for an overnight stop,you should be able to reach it in a single stopper journey,we went through the everglades,and did the journey in 10 hours,the bridges are something else...ENJOY!!!!!!
Yes indeed as chimpy says �the bridges are something else� especially the 7 mile bridge, as you leave one of the islands, all you can see is a bridge going off into the sea without an end and when your half way across you look back and cannot see land, look forward and no land. Amazing sight.