β-Arrestin-biased agonists are a new class of drugs with promising therapeutic effects. The molecular mechanisms of β-arrestin-biased agonists are still not completely identified. Here, we investigated the effect of angiotensin II (AngII) and [Sar1,Ile4,Ile8] AngII (SII), a β-arrestin-biased agonist, on ezrin–radixin–moesin (ERM) phosphorylation in NIH3T3 cells (a fibroblast cell line) stably expressing AngII type 1A receptor. ERM proteins are cross-linkers between the plasma membrane and the actin cytoskeleton and control a number of signaling pathways. We also investigated the role of Gαq protein and β-arrestins in mediating ERM phosphorylation. We found that AngII stimulates ERM phosphorylation by acting as a β-arrestin-biased agonist and AngII-stimulated ERM phosphorylation is mediated by β-arrestin2 not β-arrestin1. We also found that SII inhibits ERM phosphorylation by acting as a Gαq protein–biased agonist. We concluded that ERM phosphorylation is a unique β-arrestin-biased agonism signal. Both AngII and SII can activate either Gαq protein or β-arrestin-mediated signaling as functional biased agonists according to the type of the cell on which they act.