Unlike intracellular Ca²⁺, extracellular Ca²⁺ ([Ca²⁺]_o) has received only limited attention. [Ca²⁺]_o has profound effects on neuronal membrane potential and synaptic transmission. Physiological conditions like sensory stimulation, sleep-wake transitions and pathological conditions like seizures, ischemia are reported to decrease [Ca²⁺]_o. However, these data are obtained from a single point analysis using a Ca²⁺ electrode and lack spatiotemporal information of [Ca²⁺]_o changes. To understand processes shaping local and global [Ca²⁺]_o change involved in regulating physiological and pathological neuronal activity, we need an imaging technique that provides higher spatiotemporal resolution. Thus, we developed a label-free [Ca²⁺]_o image sensor (CIS) with a time resolution of a few tens of milliseconds at 23.55 mm pitch of 128 x 128 pixel. The CIS is highly selective to Ca²⁺ but not to other cations within wide dynamic range (from 100 mM to 100 mM). We used CIS for the imaging of [Ca²⁺]_o in acute hippocampal slices. Stimulation with neurotransmitter glutamate (Glu), decreased [Ca2+]o to around 800 mM within 10 s, which gradually returned to the baseline level (2 mM) with slow kinetics (5 min). The Glu-evoked [Ca²⁺]_o decrease was higher in CA1 and DG compared to CA3, and was inhibited by a NMDA receptor antagonist D-APV but not AMPA receptor antagonist CNQX. NMDA mimicked the Glu-evoked [Ca²⁺]_o decrease and, again was inhibited by D-APV. These findings suggest that Glu acts on neuronal NDMA receptors to reduce [Ca²⁺]_o with different spatiotemporal patterns, reflecting differences in NMDA receptors distribution. Our study demonstrates that a CIS can detect [Ca²⁺]_o changes associated with biological events and have broad applicability in future biological studies.