Core-sheath nanofibers are a premium material to be used in the field of controlled drug release, however, a mass-production of this kind of fibers by current spinning methods is until now limited due to the issues of nozzle clogging and high costs. In this context, a brand-new technology, named co-axial electro-centrifugal spinning (ECS), which combines the technologies of co-axial electrospinning and centrifugal spinning, was proposed to fabricate core-sheath nanofibers in large amounts. Compared with traditional co-axial electrospinning, the in-house-built co-axial ECS well addressed the nozzle cleaning problem. By means of the co-axial ECS, different kinds of core-sheath nanofibers were successfully produced. Being already extensively-applied biodegradable polymers, poly(vinyl alcohol) (PVA) and poly(l-lactic acid) (PLLA) were chosen to manufacture PVA/PLLA core/sheath nanofibers with different core-to-sheath ratios in ultra-high production rate. Also, Paclitaxel drug was loaded in the PVA core component and its release was efficiently controlled thanks to the thickness and crystallinity of the PLA sheath. The in vitro drug release mechanism studied here suggested that the drug can still release out without the existence of porous microchannels. This accessible and low-cost technology may definitely offer a new insight into the fabrication of core-sheath nanofibers, allowing more researchers to tailor functional fabrics.