DNA-encoded library (DEL) screening with encoded combinatorial chemical synthesis has emerged as a powerful approach to discover novel ligands for targets of interest. Here, we describe a complementary “digitization” workflow that encodes pre-synthesized (non-combinatorial) compounds. In this approach, a bifunctional linker is photoactivated to generate a carbene that directly inserts into the putative ligand, followed by a [3+2] cycloaddition to conjugate a unique DNA barcode. The resulting DNA-tagged compounds are pooled and screened in parallel against protein targets, and active ligands are enriched.