Calculate fuel economy from distance and fuel.
Fuel economy is measured, not estimated: fill the tank, reset the odometer, drive normally, then fill it again and divide the miles by the gallons it took. The gallons-per-100-miles line inverts the same measurement, and it is the more honest way to compare cars because mpg is a reciprocal scale — going from 15 to 20 mpg saves far more fuel than going from 40 to 45, even though both are five-mpg gains.
Economy
mpg = miles driven / gallons used
Consumption
Gallons per 100 miles = 100 / mpg; annual cost = price / mpg x annual miles
Trip computers infer consumption from injector duty cycle and are commonly optimistic by 3 to 8 percent. A tank-to-tank measurement is the reference, provided you fill to the same point both times.
At least three, averaged. A single tank is sensitive to how full the last fill was, the mix of roads driven and the weather, so one measurement can be off by several mpg.