Abstract The nervous system is as complex as difficult to probe. Innovative tools reducing the network complexity and being able to interrogate neurons are crucial to better understand its function and organization. In this study, solution‐gated graphene field effect transistors (GFETs) are combined with multi‐compartment microfluidic platform for multimodal and long‐lasting recording of neuron electrical activity. The fluidic microchannels, somatic and synaptic chambers enable to define the neuron network topology, while the graphene devices provide localized, highly sensitive, and optically transparent sensing sites. Immunofluorescence staining assesses for the healthy state and outgrowth of neurons within the microfluidic circuit, while calcium imaging demonstrates the maturation and spontaneous activity of the designed network. The efficient cell‐sensor alignment obtained by the microfluidic circuit enables to reach the highest reported signal‐to‐noise ratio for single‐units detection with GFETs, revealing additional information that can remain hidden from recordings when using conventional microelectrode arrays. Thus, the combination of graphene sensors and microfluidic circuits leverages the advantages of two state‐of‐the‐art technologies for highly efficient sensing of model neural networks. Being fully transparent and therefore compatible with optogenetic tools and high‐resolution microscopy, this novel platform can provide a versatile lab‐on‐chip for diagnosis and treatment of tomorrow.