Interstate 75 begins its northerly journey at an interchange with State Road 924 and State Road 826 in Hialeah, a suburb of Miami. After intersections with Interstate 595 and the Florida's Turnpike, the interstate leaves the Miami metropolitan area and turns westward to travel along Alligator Alley, which brings the freeway to the Gulf Coast and Naples, where it again heads north. Passing through Bonita Springs, Fort Myers, and Sarasota, Interstate 75 encounters a series of construction projects that will increase the lane count from two lanes in each direction to three. The freeway enters the Tampa Bay metropolitan area after an interchange with Interstate 275 northbound, which handles St. Petersburg-bound traffic. Within the Tampa metro are two more major junctions: One with Interstate 4 and another as Interstate 275 traffic defaults back onto northbound. The freeway proceeds to enter rural portions of Pasco, Hernando, and Sumter counties on its way to Ocala and Gainesville. At Lake City, transcontinental Interstate 10 meets Interstate 75, providing access to Tallahassee and Jacksonville; and a few miles later, the interstate exit the sunshine state into southern Georgia.
Interstate 75 enters Georgia near Valdosta, and continues northward through the city of Tifton until it reaches Macon, where it intersects Interstate 16 eastbound for Savannah. For northbound traffic wishing to avoid potential congestion in Macon, Interstate 475 provides a relatively short bypass to the west of the city and Interstate 75's alignment. The freeway reaches no major junctions again until the Atlanta metropolitan area. The first metro freeway met is Interstate 675, which is quickly followed by the Atlanta bypass, Interstate 285. The road shares is multiplexed with Interstate 85 through the central business district of Atlanta. After the split, Interstate 75 beelines for Interstate 285 and the suburb of Marietta. North of Marietta, the final major junction in the Atlanta metro area is with Interstate 575. The freeway then traverses the rugged northeastern Georgia terrain as it heads towards Chattanooga, Tennessee.
The freeway enters Tennessee directly in the Chattanooga metropolitan area, where it intersects with Interstate 24. Exiting Chattanooga to the northeast, Interstate 75 does not meet any other highways until it is multiplexed with Interstate 40 and heads eastbound. Together, they enter the outskirts of Knoxville, where Interstate 75 multiplexes itself with a different road, this time Interstate 640, but only for a short time. When the two meet Interstate 275, Interstate 75 becomes its own freeway and heads north towards the Kentucky border.
Interstate 75 continues northbound in Kentucky without any major cities or junctions until reaching Lexington, where it briefly runs coterminiously with Interstate 64 before splitting off for Cincinnati, Ohio. En route, near Walton, Interstate 71 nouthbound merges onto Interstate 75, making for yet another multiplexed portion of freeway. Interstate 275 -- which is the southern half of the Cincinnati beltway, is then intersected by Interstate 71/75. After passing through the suburb of Covington, the freeway crosses the Ohio River via the Brent Spence Bridge and continues into Cincinnati.
Immediately after entering Cincinnati, Interstate 71 separates from Interstate 75, taking a more easterly routing through the city, while Interstate 75 remains generally northbound throughout the metropolitan area. Interstate 74 westbound, Ohio State Road 562 eastbound, and Ohio State Road 126 all intersect the freeway as it makes its way northward. In the Arlington Heights neighborhood of Cincinnati, Interstate 75 sees a carriageway split for a few miles. After another interchange with the Interstate 275 beltway, the freeway leaves the metropolitan area and heads towards Dayton, where Interstate 675 and Interstate 70 have interchanges. After exiting Dayton, Interstate 75 makes its way northbound through Ohio -- managing to miss many of the state's major cities until Toledo, which is located very close to the Michigan border. Interstate 475 is met first in that city, and then the cross-country Interstate 90/Interstate 80 toll road duplex. Interstate 280 is the last major junction in Ohio; the freeway crosses into Michigan soon afterwards.
Interstate 75 hugs the western shore of Lake Erie upon entering Michigan -- until about Monroe, when it heads westward and prepares to enter Detroit and its surrounding suburbs. Yet another Interstate 275 is met as the freeway goes deeper into the Detroit metropolitan area, and no other major junctions are present until downtown. Once downtown, Interstate 75 meets the Ambassador Bridge to Windsor, Canada, Interstate 375 (Chrysler Freeway), Interstate 94, and M-8 (Davison Freeway). Interstate 696 also intersects I-75 in the northern metro area. When the freeway reaches Pontiac, there is a junction with M-59; and further north in Flint, the interstate meets Interstate 475 and Interstate 69. The freeway then heads north towards Saginaw, where Interstate 675 acts as a spur route into the city. Further north in Bay City, the major junction of US 10 exists, providing access to Midland as well as downtown Bay City. At Mackinaw City, I-75 crosses the Mackinac Bridge to reach the Upper Peninsula, where the road terminates at the Canadian border in Sault Ste. Marie.