Modern formulation in a wide variety of lubricants including engine oils and transmission fluids is designed to control friction through film-forming tribochemical reactions induced by the functional additives mixtures. Although many cases on the synergistic or antagonistic effects of additives on friction have been reported, their mechanisms are poorly understood. This study focused on the influences of metallic detergents on tribochemical reactions. We examined the mechanical properties of detergent-containing lubricants confined at a single-asperity contact and their contributions to tribochemical phenomena. We found that detergents enlarged the confinement space required for generating repulsive force and shear resistance. This means that these detergents provide steric effects under nanoconfinement at interfacial contacts. These detergents reduced friction synergistically with molybdenum dithiocarbamate (MoDTC), which is a widely used friction modifier additive that forms a slippery tribofilm. When detergents and MoDTC were mixed together in lubricants, their friction coefficient was very well correlated with the steric size. The steric size was similar to the spatial particle size of detergents measured by dynamic light scattering experiments. This suggested that steric effects were based on mechanical interference between contacting surfaces. We also found a correlation between steric size and synergy with MoDTC on non-detergent nanoparticles in the same way as detergents. These results led us to the conclusion that tribochemical reactivity of the lubricants containing detergents and MoDTC was enhanced by the steric effects under nanoconfinement. We consider that the microscopic friction between nanoparticles and solid surfaces helps MoDTC receive frictional energy to form slippery tribofilms, resulting in a synergistic reduction in friction. Such concept based on steric effects may be applicable to control many other tribochemical reactions.