In my experience I've found those fuel mileage calculators to be pretty accurate.
I swapped my truck with my Uncle's '05 Grand Cherokee a few years ago for a week to go down to Panama City Beach for spring break.
5 adults and loaded with luggage, we averaged 18 mpg round trip, including some driving around the area. I reset the fuel mileage gauge and the trip meter. We left with a full tank.
After all was said and done, the computer calculated 17.8 mpg, while the final math was 18 even. I'd say that's pretty accurate.
The same may not be true for all vehicles though.