Abstract: To accelerate the discovery of focal adhesion kinase (FAK)-targeting proteolysis-targeting chimera (PROTAC) degraders and shorten the synthesis and screening cycle, an automated modular click chemistry strategy was implemented using the in-house “Easy-pack” platform. Two series comprising 12 novel FAK degraders, the cereblon(CRBN)-recruiting FM2-A series and the von Hippel-Lindau disease tumor suppressor(VHL)-recruiting FM2-B series, were constructed. Western blot-based screening showed that most derivatives induced concentration-dependent FAK degradation. FM2-A6 exhibited the highest activity, achieving FAK degradation rates of 50.3% and 52.0% at 0.1 and 1 μmol/L, respectively, though its degradation efficacy was slightly lower than that of the positive control. FM2-A6 also potently inhibited FAK kinase activity, with an IC₅₀ value of 2.32 nmol/L. Mechanistic studies demonstrated that FM2-A6-mediated FAK degradation depended on FAK engagement, CRBN recruitment, and the ubiquitin-proteasome system. Molecular modeling indicated that FM2-A6 could simultaneously engage FAK and CRBN through interactions with key residues, including CYS502, HIS378, and TRP380. Physicochemical property predictions suggested that, compared with the reference compound GSK215, FM2-A6 exhibited reduced lipophilicity and moderately improved solubility, though limitations common to PROTACs, including high molecular weight and poor predicted oral absorption, remained. Structure-activity relationship analysis indicated that modular combination of ligands and linkers could effectively modulate degradation activity. Collectively, this study demonstrates the feasibility of combining automated rapid assembly with activity screening for the discovery of FAK degraders and provides experimental and computational support for subsequent lead optimization.