Nitrogen (N) is a critical nutrient for plants but is often distributed unevenly in the soil. Plants therefore have evolved a systemic mechanism by which N starvation on one side of the root system leads to a compensatory upregulation of nitrate uptake on the other side. However, the molecular components underlying this long-distance signaling, called systemic N-demand signaling, have long remained elusive. We identified that N starvation-induced small 15-amino-acid secreted peptide, CEP (C-terminally encoded peptide), acts as a root-derived ascending N-demand signal to the shoot via xylem. CEP is recognized in the shoot by specific LRR-receptor kinase, CEPR (CEP receptor), that leads to the production of non-secreted polypeptide, CEPD (CEP downstream), as a secondary signal. CEPD acts as a shoot-derived descending signal to the root via phloem and ultimately upregulates nitrate transporter NRT2.1 gene in the roots. Thus, CEP family peptides induced on one side of the roots by local N starvation is able to mediate upregulation of NRT2.1 in the distant part of the roots. Our findings provide new insights into the molecular basis of plant adaptation to a dynamically fluctuating N environment.