Covalent inhibitors and chemical probes targeting ligandable cysteine residues have emerged as powerful tools for drug discovery and proteomics. In this study, we introduce vinyl phosphonamidates (VPAs) as a novel class of latent cysteine electrophiles and assess their reactivity, selectivity, and potential for developing covalent inhibitors. Compared to well-established chloroacetamide and acrylamide electrophiles, VPAs exhibit a significantly lower intrinsic reactivity toward the model thiol glutathione. Moreover, VPA-derived covalent fragments displayed only very limited nonspecific reactivity in human cell lysate. Encouraged by these results, we developed VPA-functionalized derivatives of the FDA-approved covalent inhibitors Afatinib and Ibrutinib and evaluated their ability to engage the target protein by gel-based and mass spectrometry-based activity-based protein profiling (ABPP). Compared to commonly employed Michael acceptor-based electrophilic groups, VPA-functionalized drug ligands displayed significantly less off-targets while maintaining inhibitor efficiency. Furthermore, we leveraged the modular nature and accessibility of VPAs to develop a bifunctional proteolysis targeting chimera (PROTAC) for targeted protein degradation. The demonstrated selectivity and modularity, as exemplified by the incorporation of various ligands on the phosphorus O-substituent, of the vinyl phosphonamidate group as a cysteine-directed electrophile highlight its ability to expand the chemical space in the development of covalent inhibitors with a favorable proteome-wide reactivity profile.