To be perfectly clear, a train that does this typically isn’t carrying any freight. Trains that carry one ton of freight get just below 500 mpg. Moving freight by train is about 3 times more fuel efficient than doing so by highway.
You might be thinking 500 mpg sounds more like 20 times the fuel efficiency of highway freight, but the 500 mpg figure is just for one ton of cargo. Both trains and, for example, the trucks you see carrying a dozen or so cars, carry many tons of freight.
One of the benefits of train transport, aside from the fuel efficiency, is the reduced gas emissions. Fuel efficiency for trains is measured in terms of ton-miles, because of the variance in length and weight of the trains. Ton miles are simply the amount of distance traveled with an amount of weight with the amount of fuel used (in gallons).
In 2009, most CSX trains (an American company) averaged 468 miles per gallon per ton. Since 2000, CSX has spent $1.5 billion on improving locomotive fuel efficiency and reducing emissions alone.