In Kentucky, I-71 begins east of Downtown Louisville at the Kennedy Interchange, where it meets I-64 and I-65. This interchange is sometimes called "Spaghetti Junction". From Louisville, it roughly follows the Ohio River in a diagonal path to Northern Kentucky, across the river from Cincinnati. I-71 is concurrent with Interstate 75 from Walton to the Ohio state line.
In Cincinnati, I-75 splits from I-71 onto Fort Washington Way. From there, I-71 heads in a general north east direction through urban Cincinnati and into its surrounding suburbs. It continues northeast until it reaches South Lebanon, Ohio, where it begins cutting east across the flat plains of southwest Ohio to Grove City, just south of Columbus. I-71 then intersects with the bypass I-270 before heading north into Columbus, where it junctions I-70 and exits out of Columbus. The highway continues north until near Delaware, where it again turns northeast. Beginning its path to Cleveland, I-71 enters the rolling farm country on the edges of the Allegheny Plateau. It continues in this fashion to Lodi/Westfield Center and its junction with I-76. Heading north to Medina, it meets the terminus of I-271. The highway then continues north into urban Cuyahoga County and Cleveland's suburbs, intersecting the Ohio Turnpike/I-80. Passing Cleveland Hopkins International Airport, I-71 meets I-480 and enters Cleveland's west side, continuing on to downtown. It junctions with State Route 176 and terminates at Interstate 90 on the innerbelt.