Slip of pyramidal <c + a> dislocations in hexagonal close-packed (hcp) crystals is a requisite for accommodation of homogeneous c-axis deformation. However, fundamental aspects of the formation and slip of pyramidal dislocations, including the formation mechanism, dissociation, core structure and slip features, are still poorly characterized. In this study, large-scale molecular dynamics simulations reveal that the formation of <c + a> dislocations in magnesium single crystals during c-axis loading occurs by sequential nucleation of leading and trailing partial dislocations on pyramidal I planes, owing to their lower lattice resistance to shear compared with pyramidal II planes. Local shuffling on pyramidal I planes was also found to be a mediating mechanism for nucleation and slip of pyramidal I <c + a> dislocations. Subsequent transition of pyramidal I slip to pyramidal II planes is achieved either by cross-slip of screw-segments or by cooperative slip of edge-segments on two equal and alternative pyramidal I planes. Consequently, at moderate strains, slip occurs predominantly on pyramidal II planes, in excellent agreement with experimental observations. Climb was also observed for both pyramidal I and pyramidal II <c + a> dislocations even at very low temperatures. This results in production of an abundance of interstitials and vacancies in the crystal. Formation of pyramidal I <a> dislocations by reaction of two pyramidal I <c + a> dislocations was also observed. These findings uncover unique features of pyramidal slip in low-symmetry hcp magnesium crystals and have important implications for understanding their distinct mechanical behavior and also for improving their performance.