What US region was once a separate country?

Answer 1

You should specify what exactly it is that you mean by "region".

I'll give you a quick slew off the top of my head and see if I hit home:

-Texas was once an independent Country.

-All of the South West from Oregon to California to the Western Edge of Texas was once the sovereign territory of Mexico.

-Hawaii was once ruled by a monarchy, before annexation by the U.S.

-----

in addition:

California used to be the Independant Republic of California before becoming a state on September 9th 1850 after Mexico ceded it to the United States.

Puerto Rico and Guam were both colonized by Spain and accuired by the United States in 1898 as part of the Treaty of Paris.

A large region of land (828,800 square miles!) claimed by France was purchased by the United States for only 15 million dollars (that's only $18.10 per square mile!), and is known today as the Louisiana Purchase.

The land purchased contained all of present-day Arkansas, Missouri, Iowa, Oklahoma, Kansas, Nebraska, parts of Minnesota that were west of the Mississippi River, most of North Dakota, nearly all of South Dakota, northeastern New Mexico, the portions of Montana, Wyoming, and Colorado east of the Continental Divide, and Louisiana west of the Mississippi River, including the city of New Orleans.

It could be argued that the whole of the North American Continent was once inhabited by several tribes of Native North Americans before being colonized by Spain, France and England.