1. Take it easy when accelating from a standstill, and if you have a manual transmission, downshift when approaching traffic lights. It will help save your brakes too.
2. Make sure you push the choke knob in all the way once the engine has warmed up.
3. Make sure your tires are not low on air. I inflate mine to 35 psi.
4. Check for any air leaks in your intake manifold. I experienced the problem frequently with the inline 6.
I was able to get around 17-18 mpg on the highway with a 250 and a 3 on the tree in a 1966 C-10, and it was original. I get about the same with my current 1966 C-10 with a 283 and a Powerglide transmission.
