A continuous Chinese hamster ovary (CHO) cell culture process comprised of a highly proliferative N‐1 perfusion bioreactor utilizing a hydrocyclone as a cell retention device linked to a production continuous‐flow stirred tank reactor (CSTR) is presented. The overflow stream from the hydrocyclone, which is only partially depleted of cells, provides a continuous source of high viability cells from the N‐1 perfusion bioreactor to the 5–20 times larger CSTR. Under steady‐state conditions, this linked‐bioreactor system achieved a peak volumetric productivity of 0.96 g/L/day, twofold higher than the optimized fed‐batch process. The linked bioreactor system using a hydrocyclone was also shown to be 1.8–3.1 times more productive than a dual, cascading CSTR system without cell retention. Hydrocyclones are small and simple devices that alleviate fouling and scale‐up concerns associated with conventional perfusion methodologies. We have demonstrated an N‐1 perfusion bioreactor utilizing a hydrocyclone for cell retention linked to a 5–20× larger production continuous‐flow stirred tank reactor operating at a steady state. This linked bioreactor system reaches 2× the volumetric productivity of the optimized fed‐batch process while enabling the use of legacy manufacturing infrastructure up to 10,000 L.