Hypoxic ventilatory responses differ between rodent strains, suggesting a genetic contribution to inter-individual variability. However, hypoxic ventilatory responses consist of multiple time-dependent mechanisms that can be observed in different respiratory motor outputs. We hypothesized that strain differences would exist in discrete time dependent-mechanisms of the hypoxic response and, further, that there may be differences between hypoglossal and phrenic nerve responses to hypoxia. Hypoglossal and phrenic nerve responses were assessed during and following a 5-min hypoxic episode in anesthetized, vagotomized and ventilated rats from four inbred strains: Brown Norway (BN), Fisher 344 (FS), Lewis (LW), and PVG. During baseline, burst frequency was higher in PVG than LW rats (p<0.05), phrenic burst amplitude was higher in PVG versus other strains (p<0.05), and hypoglossal burst amplitude was higher in PVG and BN versus FS and LW (p<0.05). During hypoxia, burst frequency did not change in BN or LW rats, but increased in PVG and FS rats. The phrenic amplitude response was smallest in PVG versus other strains (p<0.05) and the hypoglossal response was similar among strains. Short-term potentiation post-hypoxia was slowest in FS, and fastest in LW rats (p<0.05). Post-hypoxia frequency decline was absent in PVG, but was observed in all other strains. Augmented breaths were observed during hypoxia in FS rats only. Thus, genetic differences exist in the time-domains of the hypoxic response and these are differentially expressed in hypoglossal and phrenic nerves. Further, genetic diversity observed in hypoxic ventilatory responses in unanesthetized rats may arise from multiple neural mechanisms.