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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 ∼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.