The Zn2+ stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn2+ concentration (CZn2+ex). This elevation of CZn2+ex regulates the neurotransmission and facilitates the fibrilization of amyloid‐β (Aβ). However, the exact CZn2+ex surrounding neurons under (patho)physiological conditions is not clear and the connection between CZn2+ex and the Aβ fibrilization remains obscure. Here, a silicon nanowire field‐effect transistor (SiNW‐FET) with the Zn2+‐sensitive fluorophore, FluoZin‐3 (FZ‐3), to quantify the CZn2+ex in real time is modified. This FZ‐3/SiNW‐FET device has a dissociation constant of ≈12 × 10−9m against Zn2+. By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ‐3/SiNW‐FET, the CZn2+ex elevated to ≈110 × 10−9m upon stimulation with α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). Blockers against the AMPA receptor or exocytosis greatly suppress this elevation, indicating that the Zn2+ stored in the synaptic vesicles is the major source responsible for this elevation of CZn2+ex. In addition, a SiNW‐FET modified with Aβ could bind Zn2+ with a dissociation constant of ≈633 × 10−9m and respond to the Zn2+ released from AMPA‐stimulated neurons. Therefore, the CZn2+ex can reach a level high enough to bind Aβ and the Zn2+ homeostasis can be a therapeutic strategy to prevent neurodegeneration.