The cannabinoid receptor 1 (CB₁R) is required for body weight homeostasis and normal gastrointestinal motility. However, the specific cell types expressing CB₁R that regulate these physiological functions are unknown. CB₁R is widely expressed, including in neurons of the parasympathetic branches of the autonomic nervous system. The vagus nerve has been implicated in the regulation of several aspects of metabolism and energy balance (e.g., food intake and glucose balance), and gastrointestinal functions including motility. To directly test the relevance of CB₁R in neurons of the vagus nerve on metabolic homeostasis and gastrointestinal motility, we generated and characterized mice lacking CB₁R in afferent and efferent branches of the vagus nerve (Cnr1^flox/flox; Phox2b–Cre mice). On a chow or on a high-fat diet, Cnr1^flox/flox; Phox2b–Cre mice have similar body weight, food intake, energy expenditure, and glycemia compared with Cnr1^flox/flox control mice. Also, fasting-induced hyperphagia and after acute or chronic pharmacological treatment with SR141716 [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole carboxamide] (CB₁R inverse agonist) paradigms, mutants display normal body weight and food intake. Interestingly, Cnr1^flox/flox; Phox2b–Cre mice have increased gastrointestinal motility compared with controls. These results unveil CB₁R in the vagus nerve as a key component underlying normal gastrointestinal motility.