The triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial innate immune receptor associated with a lethal form of early, progressive dementia, Nasu-Hakola disease, and with an increased risk of Alzheimer’s disease. Microglial defects in phagocytosis of toxic aggregates or apoptotic membranes were proposed to be at the origin of the pathological processes in the presence of Trem2 inactivating mutations. Here, we show that TREM2 is essential for microglia-mediated synaptic refinement during the early stages of brain development. The absence of Trem2 resulted in impaired synapse elimination, accompanied by enhanced excitatory neurotransmission and reduced long-range functional connectivity. Trem2−/− mice displayed repetitive behavior and altered sociability. TREM2 protein levels were also negatively correlated with the severity of symptoms in humans affected by autism. These data unveil the role of TREM2 in neuronal circuit sculpting and provide the evidence for the receptor’s involvement in neurodevelopmental diseases. Display omitted •Lack of TREM2 results in lower microglia activation during early brain development•TREM2 is required for microglia-dependent synapse elimination•Adult mice lacking TREM2 display sociability defects and altered brain connectivity•TREM2 protein is reduced in patients affected by autism TREM2 is a microglial innate immune receptor whose functions during brain development are still unknown. Filipello et al. demonstrate that TREM2 is essential for microglia to eliminate supernumerary synapses in the developing brain. TREM2 protein was also reduced in autistic patients, suggesting that the receptor may be involved in neurodevelopmental diseases.