The separation of enantiomers using high-performance chromatography technologies represents great importance and interest. In this aspect, β-cyclodextrin (β-CD) and its derivatives have been extensively studied as chiral stationary phases (CSPs). Nevertheless, β-CD that was immobilized on a traditional matrix often exhibited low stabilities and limited operating ranges. Recently, covalent organic frameworks (COFs) with highly ordered nanopores are emerging as promising CSPs for enantioseparations, but their practical applications are still hampered by the difficulty of monomer and COF synthesis. Herein, two β-CD-driven COFs are synthesized via a fast and facile plasma-induced polymerization combined postsynthesis modification strategy. The precisely defined COF channels enhanced the accessibility of the accommodated β-CD to the analytes and acted as robust protective barriers to safeguard the β-CD from harsh environments. Therefore, the β-CD-modified COFs can be potentially general CSPs for extensive enantioseparation in both gas chromatography and high-performance liquid chromatography, and a wide range of racemates were separated. Compared to the commonly employed commercial chiral columns, these COF-based columns exhibited comparable resolution capability and superior application versatility. This work integrates the advantages and overcomes the defects of COFs and β-CD, thus advancing COFs as platforms for chiral selector modification and giving great promise for practical chromatographic enantioseparation.