Questions remain concerning the genesis and geological setting of the ultramafic rock-associated mineralization of the Sykesville District, Maryland, USA, which is located in the mid-Atlantic Appalachians. Best described as a mafic-ultramafic VMS deposit, the ores are polymetallic Fe-Cu-Co-Ni-Zn sulfides hosted within an iron oxide-quartz rock and tectonic mélange that is everywhere in close proximity to ultramafic rocks. Optical microscopy, EDS, and WDS analyses of minerals in thin sections and epoxy mounts of rocks from drill core were performed to aid in understanding the deposit’s formation and defining exploration vectors relevant to similar deposits. Monazite dating has been performed by WDS yielding dates broadly consistent with the Taconian orogeny. The mineralization of the Sykesville District contains textures possibly indicative of seafloor deposition in an environment analogous to an oceanic core complex. These markers may hold promise for identifying the timing, paragenesis, and lithological and mineralogical associations of other Appalachian VMS deposits.