Poly(ether ether ketone) (PEEK) is a promising material in biomedical engineering due to its suitable mechanical properties and excellent chemical resistance and biocompatibility. However, the biological inertness of PEEK limits its applications. In this study, we developed a facile approach of immersion to generate a biocompatible and bioactive PEEK that induced osteodifferentiation. First, micro-pores on the surface of PEEK were introduced by concentrated sulfuric acid and subsequent water immersion, followed by the hydrothermal treatment to reduce residual sulfuric acid. Subsequently, the sulfonated PEEK surface was activated by the oxygen plasma treatment and then coated with a poly(dopamine) (PDA) layer by immersion into the dopamine solution. Finally, the tripeptide Arg-Gly-Asp (RGD) was integrated onto the PDA-coated surface of PEEK by immersion into the RGD peptide solution. The surface characteristics (physical chemistry and biological properties) and the ability to form bonelike apatite were systematically investigated by scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle analysis, the Archimedes' fluid saturation method, ellipsometry, a quartz crystal microbalance with dissipation monitoring, cell proliferation, real-time reverse transcription polymerase chain reaction analysis, alizarin red staining, immunocytochemistry staining, and simulated body fluid immersion. Collectively, the modified PEEK showed a significantly improved ability to promote cell proliferation, osteogenic differentiation, and bonelike apatite formation in vitro as compared to the PEEK control. These results demonstrate that combined facile surface modifications for PEEK enhance its bioactivity and biocompatibility, and induce osteodifferentiation. This study presents a strategy for broadening the use of PEEK in the application of orthopedic implants and could be industrially scalable in future.