•  Proteins are more satiating than fats or lipids. Proteins are built by the 20 proteogenic amino acids. •  Here, we identified l‐arginine, l‐lysine and l‐glutamic acid as the most potent anorectic amino acids in rats. •  l‐Arginine and l‐glutamic acid require intact neurons in the area postrema to inhibit food intake, whereas l‐lysine requires intact afferent fibres of the vagus nerve. All three mediate their effect by the blood stream. •  All three amino acids induce gastric distension by delaying gastric emptying and inducing secretion. However, the gastric phenotype does not mediate the anorectic response. •  These results unravel amino acid‐specific mechanisms regulating digestion and eating behaviour and thereby contribute to the understanding of nutrient sensing in vivo. Abstract  To maintain nutrient homeostasis the central nervous system integrates signals that promote or inhibit eating. The supply of vital amino acids is tuned by adjusting food intake according to its dietary protein content. We hypothesized that this effect is based on the sensing of individual amino acids as a signal to control food intake. Here, we show that food intake was most potently reduced by oral l‐arginine (Arg), l‐lysine (Lys) and l‐glutamic acid (Glu) compared to all other 17 proteogenic amino acids in rats. These three amino acids induced neuronal activity in the area postrema and the nucleus of the solitary tract. Surgical lesion of the area postrema abolished the anorectic response to Arg and Glu, whereas vagal afferent lesion prevented the response to Lys. These three amino acids also provoked gastric distension by differentially altering gastric secretion and/or emptying. Importantly, these peripheral mechanical vagal stimuli were dissociated from the amino acids’ effect on food intake. Thus, Arg, Lys and Glu had a selective impact on food processing and intake suggesting them as direct sensory input to assess dietary protein content and quality in vivo. Overall, this study reveals novel amino acid‐specific mechanisms for the control of food intake and of gastrointestinal function.