Herein, we present an unprecedented azine‐limited C5−H polyfluoroarylation of 2‐aminopyridines enabled by a transient and electron‐deficient perfluoroaryl‐Pd species via C−H/C−H coupling. The protocol further allows C3(5)−H polyfluoroarylation of 2‐alkoxypyridines guided by sterics and electronics for the first time. The late‐stage C−H functionalization of drugs, drug derivatives, and natural product derivatives and synthesis of C5‐aryl drug derivatives further demonstrated the method's utility. The preliminary mechanistic studies reveal that the synergistic combination of the bulky yet electrophilic perfluoroaryl‐Pd species and the partial nucleophilicity of the C5‐position of 2‐amino/alkoxy‐pyridines is the origin of reactivity and selectivity. Importantly, the first experimental evidence for the role of diisopropyl sulfide is provided.