The availability of the railroad and freight service provided by the Fort Worth and Denver City Railroad contributed to the city's growth as a cattle marketing center in the late 19th century.

Amarillo is the regional economic center for the Texas Panhandle,and is economically important to Eastern New Mexico and the Oklahoma Panhandle.

The city was once the self-proclaimed Helium Capital of the World for having one of the country's most productive helium fields. The city is also known as The Yellow Rose of Texas (as the city takes its name from the Spanish word for yellow), and most recently Rotor City, USA for its V-22 Osprey hybrid aircraft assembly plant.

Amarillo operates one of the largest meat packing areas in the United States. Pantex, the only nuclear weapons assembly and disassembly facility in the country, is also a major employer. The attractions Cadillac Ranch and Big Texan Steak Ranch are located adjacent to Interstate 40. The Two RV Gypsies visited both of these famous places and more.

The Big Texan Steak Ranch feeds almost half a million people each year from all over the world. It has been featured in countless TV shows, movies, magazines, and newspapers throughout the United States, Europe, Asia and Australia. Countless movies and sitcoms have featured or parodied the World Famous FREE 72-oz. steak dinner (if eaten in 1 hour).