Carbon fiber reinforced polymer (CFRP) structure has anisotropy and non-uniformity, and processing is prone to fiber tearing, delamination, debonding, and other damages. In this paper, we propose to mill CFRP using a cold plasma jet (CPJ) in combination with nanofluidic minimal quantity lubrication (NMQL) cooling medium to achieve high-precision and low-defect milling of CFRP. CPJ is rich in active particles that can regulate the surface wettability and mechanical properties of CFRP materials. Firstly, the droplet method and XPS analyses showed that CPJ could reduce the contact angle of bio-based nano-lubricants by enhancing the polar groups on the CFRP surface, indicating that CPJ could facilitate the rapid penetration of cutting fluids. Then, the nanoindentation and nano-scratching experiments revealed that CPJ can lead to an increase in both surface hardness and modulus of elasticity of CFRP, as well as improve the support properties of the resin substrate, which enhances the fracture properties of carbon fibers. Finally, milling tests were conducted on CFRP materials with different fiber orientations under five lubrication methods, namely, Dry, N 2, CPJ, NMQL, and CPJ coupled NMQL (CPJNMQL), to study the effect and mechanism of CPJNMQL lubricant on CFRP with different fiber directions. The results indicate that under CPJNMQL lubrication conditions, the milling force and surface roughness are greatly reduced, defects such as fiber debonding, bending, and tearing on the machined surface are effectively reduced, and the life of milling tools can be improved, proving that high-precision and high-quality milling of CFRPs with different fiber orientations can be achieved under CPJNMQL conditions.