In-depth studies of the etiology and consequences of brain damage induced by chronic prenatal hypoxia are now urgently needed to improve the therapeutic strategies and reinforcing the adaptive capacity of nerve cells to oxygen deficiency. Here, we analyzed the characteristics of spontaneous calcium activity of primary hippocampal cultures obtained from mouse embryos exposed to chronic prenatal hypoxia in a late period of development in vitro (DIV 15 – DIV 21) and the adaptive capabilities of neuron-glial networks to the acute hypoxic injury. Chronic hypoxic stress caused several delays in the functional development of primary hippocampal cultures. On DIV 15, the cultures exhibited the spontaneous calcium activity with a decreased number of active cells and duration of Ca2+ oscillations. The reduced values of network characteristics (DIV 15) in the presence of partial destruction of the functional architecture of neuronglial networks with a reduced force of correlated connections between cells during entire observation period were also shown. Chronic hypoxic stress altered the functional culture's response to acute oxygen deficiency. On day 7 after acute hypoxia modelling, against the background of significant decrease in the number of functionally active cells, the frequency and duration of Ca2+ oscillations did not differ from the intact values. Nevertheless, significant decrease in the network characteristics accompanied by substantial rearrangements in the functional architecture of neuron-glial networks indicate the death of significant part of the network elements and increase the risk of aggravation the synaptic transmission impairments leading to loss of network functionality in more distant post-hypoxic period.