We report here a low-cost, rapid-prototyping, and beehive-like multilayer polymer microfluidic device for ultrahigh-throughput blood plasma separation. To understand the device physics and optimize the device structure, the effect of cross-sectional dimension and operational parameter on particle focusing behavior was explored using a single spiral microchannel device. Then, the blood plasma separation performance of the determined channel structure was validated using the blood samples with different hematocrits (HCTs). It was found that a high separation efficiency of 99% could be achieved using the blood sample with an HCT of 0.5% at a high throughput of 1 mL/min. Finally, a multilayer microfluidic device with a novel beehive-like multiplexing channel arrangement was developed for ultrahigh-throughput blood plasma separation. The prototype device could be fabricated within similar to 1 hour utilizing the laser cutting and thermal lamination methods. The total processing throughput could reach up to 72 mL/min for 0.5% HCT sample with a plasma separation ratio close to 90%. Our device may hold potentials for the ultrahigh-throughput separation of blood plasma from large volume blood samples for downstream disease diagnosis.