We quantify the spatial distributions of dense cores in three spatially distinct areas of the Orion B star-forming region. For L1622, NGC 2068/NGC 2071, and NGC 2023/NGC 2024, we measure the amount of spatial substructure using the Q-parameter and find all three regions to be spatially substructured (Q < 0.8). We quantify the amount of mass segregation using MSR and find that the most massive cores are mildly mass segregated in NGC 2068/NGC 2071 ( MSR ∼ 2), and very mass segregated in NGC 2023/NGC 2024 ( MSR = 28 +13 −10 for the four most massive cores). Whereas the most massive cores in L1622 are not in areas of relatively high surface density, or deeper gravitational potentials, the massive cores in NGC 2068/NGC 2071 and NGC 2023/NGC 2024 are significantly so. Given the low density (10 cores pc −2 ) and spatial substructure of cores in Orion B, the mass segregation cannot be dynamical. Our results are also inconsistent with simulations in which the most massive stars form via competitive accretion, and instead hint that magnetic fields may be important in influencing the primordial spatial distributions of gas and stars in star-forming regions.