In Reddick US 441 continues to the northwest, serving as the northern terminus of CR 25A. From there it intersects CR 318, which provides access to I-75 in Irvine to the west and Salt Springs in Ocala National Forest to the east. The road then runs through communities such as Orange Lake and McIntosh, where it passes through the McIntosh Historic District before crossing the Marion-Alachua County Line near the town of Evinston. It passes by a turnoff to Cross Creek before entering Micanopy, then runs across Paynes Prairie Preserve State Park and goes through Gainesville as 13th Street, serving as the eastern edge of the University of Florida campus. After intersecting SR 331 and later SRs 24A-226, State Road 24 joins US 441 in a brief concurrency until it reaches State Road 26 and turns east. US 441 continues north as it becomes the western terminus of State Road 120, then intersects State Road 222 before curving to the northwest and finally joining State Road 20, thereby converting it into an additional hidden state road. At the intersection of SR 121, the "DeSoto Trail" moves from SR 121 to US 441. In Alachua, US 441 intersects with SR 235, and then runs under an interchange with Interstate 75 (Exit 399), with quarter-cloverleaf interchanges on the northeast and northwest corners.