North of Romeo, the trunkline passes through agricultural areas of The Thumb region of the state. M-53 crosses into Lapeer County south of Almont. Further north, Van Dyke Road meets I-69 in Imlay City, running through the downtown area north of the Interstate; Imlay City is also the location of a crossing of the Canadian National Railway line that carries Amtrak's "Blue Water" service between Flint and Port Huron. In the unincorporated community of Burnside, M-53 intersects M-90. The two highways run concurrently for about a mile and a half (2.4 km) before separating. M-53 continues northward and crosses into Sanilac County near Marlette. In that city, the highway crosses a branch line of the Huron and Eastern Railway (HESR) before continuing through downtown. From Marlette northward, M-53 runs parallel to, and about a mile east of, the Sanilac–Tuscola county line. The highway follows Van Dyke Road through rural farming country past intersections with M-46 and M-81 and across the Cass River before crossing into Huron County.