The major cities that I-74 connects to include Davenport, Iowa; Peoria, Bloomington, and Champaign, Illinois; Indianapolis, Indiana; and Cincinnati, Ohio.

In the state of Iowa, I-74 runs south from I-80 for 5.36 miles (8.63 km) before crossing into Illinois on the I-74 Bridge.

In the state of Ohio, I-74 runs southeast from the Indiana border to the western segment's current eastern terminus at I-75 just north of Downtown Cincinnati.

In the state of North Carolina, as of November 2024[update], I-74 exists in several segments, starting with a concurrency with I-77 at the Virginia border.

It was uncertain why the Federal Highway Administration (FHWA) made an exception, but this might have been the result of a misinterpretation when a state highway administrator asked for Interstate designation for another section and "Future Interstate" for the section already completed that did not meet standards.

[2] Long-range plans call for I-74 to continue east and south of Cincinnati to North Carolina using SR 32 from Cincinnati to Piketon, Ohio, and then the proposed I-73 from Portsmouth, Ohio, through West Virginia (along parts of current US 52 and Future WV Route 108) to I-77.

[citation needed] The 1991 plan to build I-73 soon included an extension of I-74 from where it ended in Hamilton County to I-73 at Portsmouth, Ohio, possibly along SR 32.

[5] On August 31, 1992, the Ohio Turnpike Commission passed a resolution to study making the extension of I-74 a toll road.

These include building the bypass of Rockingham with I-73[11] and the eastern half of the Winston-Salem Northern Beltway.

The North Carolina Turnpike Authority—at the request of officials in Brunswick County—are studying whether a toll road could get the section of I-74 in that county built faster.