Powerwagondude. You're getting some good replies here and I will totally agree with many of them.

Vacuum advance, overdrive and no 273. Mileage can be obtained with cubic inches. I just went from a 3.5L LHS to a 3.8L Park Ave. Same everything but better mileage.

My truck's original 318, 2 barrel could easily get 18-21 with 25mpg straight highway recorded but it was probably an 18 second truck that could barely tow anything.

It also depends on how much power you are willing to sacrifice.

Now I went with a bigger engine, mileage is down slightly 16-19 average with a peak of straight highway at 23mpg but it's much faster, 14.8 @ 91.5 and it has enough power to make me question my tie down straps.
It's a 5.9 Magnum, carbed, stock cam and a 5 speed manual.

On the higway in 5th gear.

Just enough power to still be a fun truck.