Herpes simplex virus (HSV)-1 and HSV-2 are significant human pathogens causing recurrent disease. During infection, HSV modulates cell death pathways using the large subunit (R1) of ribonucleotide reductase (RR) to suppress apoptosis by binding to and blocking caspase-8. Here, we demonstrate that HSV-1 and HSV-2 R1 proteins (ICP6 and ICP10, respectively) also prevent necroptosis in human cells by inhibiting the interaction between receptor-interacting protein kinase 1 (RIP1) and RIP3, a key step in tumor necrosis factor (TNF)-induced necroptosis. We show that suppression of this cell death pathway requires an N-terminal RIP homotypic interaction motif (RHIM) within R1, acting in concert with the caspase-8-binding domain, which unleashes necroptosis independent of RHIM function. Thus, necroptosis is a human host defense pathway against two important viral pathogens that naturally subvert multiple death pathways via a single evolutionarily conserved gene product. Display omitted •HSV-1 and HSV-2 R1 homologs block death receptor-induced necroptosis in human cells•HSV R1 homologs disrupt RIP1-RIP3 RHIM-dependent necrosome formation•Suppression of RIP3-mediated necroptosis requires both RHIM and caspase-8-binding domains•Caspase-8 inhibition blocks apoptosis but opens a necroptotic trap door Herpes simplex virus (HSV) modulates cell death to promote infection. Guo et al. show that the HSV early protein, R1, inhibits necroptosis in human cells as a RHIM signaling competitor to disrupt RIP1-RIP3 interactions. A separate C-terminal R1 function known to inhibit caspase-8 sensitizes infected cells to necroptosis.