Nature Chemistry, Published online: 27 July 2026; doi:10.1038/s41557-026-02229-z A streamlined approach for oligonucleotide functionalization is established through direct on-support phosphitylation of the growing oligonucleotide chain, enabling coupling with bifunctional alcohols and nucleosides. This method provides access to diverse terminal and internal modifications, improves functional-group tolerance, facilitates reagent recovery and offers increased flexibility beyond current phosphoramidite strategies.