The Midcontinent Rift System (MRS) is a Late Mesoproterozoic (∼1.1 Ga) sequence of volcanic and sedimentary rocks exposed in the Lake Superior Region of North America. The MRS continues to be the focus of much research due to its economic mineral deposits as well as its archive of Precambrian life and tectonic processes. In order to constrain the post-depositional thermal history of the MRS, samples were analyzed for carbonate clumped isotope composition and organic thermal maturity. Clumped isotope values from sedimentary/early-diagenetic samples were partially reset during burial to temperatures between 68 and 75 °C. Solid-state reordering models indicate that maximum burial temperatures of 125–155 °C would reset the clumped isotope values to the observed temperature range prior to the onset of regional cooling and uplift. Clumped isotope results from late-stage veins in the White Pine Mine encompass a greater temperature range (49–116 °C), indicative of spatially variable hydrothermal activity and vein emplacement after burial temperatures fell below 100 °C during regional cooling and uplift. Clumped isotope and organic thermal maturity data do not indicate significant spatial differences in thermal history along the MRS. Observed variability in bulk organic matter composition and biomarker indices are therefore more likely a result of shifts in primary productivity or early-degradation processes. These results demonstrate that the MRS experienced a spatially consistent, relatively mild thermal history (125–155 °C) and is therefore a valuable archive for understanding the Late Mesoproterozoic environment.