Abstract Plant innate immunity mostly relies on nucleotide-binding (NB) and leucine-rich repeat (LRR) intracellular receptors to detect pathogen-derived molecules and to induce defense responses. A multi-taxa reconstruction of NB-domain associations allowed us to identify the first NB-LRR arrangement in the Chlorophyta division of the Viridiplantae. Our analysis points out that the basic NOD-like receptor (NLR) unit emerged in Chlorophytes by horizontal transfer and its diversification started from TIR-NB-LRR (TNL) members. The operon-based genomic structure of Chromochloris zofingiensis NLR copies suggests a functional origin of NLR clusters. Moreover, the transmembrane signatures of NLR proteins in the unicellular alga C. zofingiensis supports the hypothesis that the NLR-based immunity system of plants derives from a cell-surface surveillance system. Taken together, our findings suggest that NLRs originated in unicellular algae and may have a common origin with cell surface LRR receptors.