Endocannabinoids (eCBs) are retrograde lipid neuromodulators involved in many physiologically important processes, yet their release and dynamics in the brain remains largely unknown, in part due to lack of probes capable of reporting eCBs with sufficient spatiotemporal resolution. Here, we developed a new G protein-coupled receptor (GPCR) Activation Based eCB sensor GRABeCB2.0 using the human CB1 receptor fused with a circular permutated EGFP (cpEGFP). GRABeCB2.0 exhibits ~second kinetics and robust fluorescence increase in response to eCBs (ΔF/F0 ~800% to 2-AG; ~550% to AEA in neurons), and does not elicit detectable G protein and arrestin coupling. Using GRABeCB2.0, we detected evoked eCB dynamics in both cultured neurons and acute mouse brain slices. Interestingly, we also observed spontaneous compartmental eCB transients that spread ~11 μm in culture neurons, suggesting constraint local eCB signaling. By expressing GRABeCB2.0 in vivo, we readily observed foot-shock elicited and running triggered eCB transients in mouse amygdala and hippocampus respectively. Lastly, using GRABeCB2.0 in a seizure model, we observed a spreading eCB wave following a calcium wave in mouse hippocampus. In summary, GRABeCB2.0 is a powerful new probe to resolve eCB release and dynamics under physiological and pathological conditions.