Interstate 380 is a spur highway that connects U.S. Highway 20 to Interstate 80; the highway also serves to connect Cedar Rapids, Iowa, the second largest city in Iowa, to Interstate 80. The northern terminus of I-380 begins in Waterloo, Iowa while the southern terminus is with I-80 in Iowa City, Iowa. The entire length of the highway is 73.05 miles. Much of I-380 is part of the Avenue of the Saints between St. Paul, Minnesota, and St. Louis, Missouri.

South of I-80, the route then becomes US Highway 218, and is a four lane route from Iowa City to Mount Pleasant, Iowa.