There will be a sweet spot in engine vacuum at any given speed that produces the best MPG.Remove as many restrictions from the exhaust system as you can. High flow cats, a free flowing muffler, ECT. big tires burn more fuel. A well tuned engine that runs properly will also burn less fuel. Then there is gear ratio. The faster the RPMs the more fuel you will burn. So 410 gears will burn more fuel than 308s will. Add to all of this driving habits and road conditions, all play a part in MPGs. I went from 342s to 373s in my truck, and yes, I am burning more fuel. If you want good fuel mileage, pit some 273 gears in the rear end, but it will be a real dog from a dead stop.
Throttle position will dictate vacuum.
Going to a numerically lower gear won’t automatically save fuel.
In fact the opposite can be true-and that’s why lifted trucks with larger tires see a huge gain in MPG by going to numerically higher gears.