Some mafic-ultramafic intrusions in the North American Midcontinent Rift System host disseminated to massive sulfides of magmatic origin. Massive sulfides are also present in the immediate sedimentary country rocks to some of these intrusions, such as Partridge River, Tamarack, and Eagle. Our working hypothesis is that the country rock-hosted massive sulfides are also of magmatic origin. To test this hypothesis, we have carried out an integrated mineralogical, chalcophile elements, and isotopic (S-Os-Pb) study of the country rock-hosted massive sulfide samples from Partridge River, Tamarack, and Eagle. Data for the intrusion-hosted sulfides from previous studies are used for comparison. Like the intrusion-hosted massive sulfides, the country rock-hosted massive sulfides are mainly composed of pyrrhotite, pentlandite, chalcopyrite, and cubanite and have high Ni, Cu, and PGE tenors, consistent with the crystallization products of magmatic sulfide liquids. These two different types of sulfide occurrences at Partridge River are different in some chalcophile element ratios and S-Os-Pb isotopes, but such differences can be explained by different parental magmas with different degrees of crustal contamination and different R-factors during sulfide segregation. At Tamarack and Eagle, these two different types of sulfide occurrences have similar S-Os-Pb isotope compositions, but the similarity in chalcophile element compositions between them is restricted to only some of the samples. Negative Pt anomalies are more common for the country rock-hosted massive sulfide than the intrusion-hosted sulfide ores. Positive Pt anomalies are not observed in the country rock-hosted massive sulfide samples but are present in some of the intrusion-hosted sulfide ore samples. Our modeling results show that the observed similarities and differences between these two different types of sulfide occurrences in each of the deposits can be explained by a common parental magma, variable R-factors during sulfide-liquid segregation, and variable degrees of fractional crystallization of monosulfide solid solution from sulfide liquids. Given the fact that positive Pt anomalies are present in some of the intrusion-hosted sulfides ores, we suggest that the negative Pt anomalies in the country rock-hosted magmatic sulfides are due to a nugget effect or removal of early-crystallized platinum group minerals, such as sperrylite (PtAs2), from the sulfide liquids prior to their infiltration into the surrounding country rocks.