In case anyone actually wants to know the answer: it’s the plot of Cars.
The difference is literally the plot of Cars.

Highways are usually two-to-four (at the widest) lane roads that meander the US landscape. Think Route 66, dinosaur statues, mom-and-pop diners, southern gothic. There are state-level and national-level highways. Some run for a 100 miles, some, like US HWY-17, run most of the East Coast:

That red line is US HWY 17. If you follow it, you will go through tiny towns. You may hit stoplights. I kid you not, you will see spinning cows on poles. Businesses exist along highways that you are encouraged to pull over and visit. They were designed to let you see America.

Yeah.

Now, interstates were made in the 50s and were made to get people from Point A to Point B. These suckers range from four lanes to eight lanes around big cities. They cut through everything. If you want to get to a business, you have to take an exit ramp and detour. They are great for getting places fast. You can still have weird experiences on them, but usually at night, when your eyes start playing tricks on you. Or there are deer.

I-95 is a massive corridor that runs from the Florida Keys to the Canadian Border. You can see the difference just looking at the maps.

As far as writing goes:

If you want quirky character development inside the car, you’re looking for an interstate. The majority of Americans take interstates to go on road trips.

If you want mysterious and/or supernatural hijinks, you’re looking for a highway. They are weird, weird places, and they’re surprisingly easy to wind up on if you leave the interstate.

(Even in America, no one’s really sure what a freeway is. Just ignore it.)

A freeway is a term someone came up with to designate a non-tollway. It’s a highway where the norm is to NOT pay tolls. The odds of a tollway depend largely on your location, I believe. Certain states, or regions within those states, tolls are unheard of. Other places they’re everywhere. 

For example, most highways and interstates in Illinois are toll-free, but on I-88, that runs across the state into Chicago, the tolls start about Rochelle and continue all the way into Chicago. 

Most highways and interstates are free in Iowa. In fact, I can’t think of a single one that has a toll.