The current climate change, unlike previous ones, is caused by human activity and is characterized by an unprecedented rate of increase in the near-surface temperature and an increase in the frequency and intensity of hazardous weather and climate events. To survive, society must be prepared to implement adaptation strategies and measures to mitigate the negative effects of climate change. This requires, first of all, knowledge of how the climate will change in the future. To date, mathematical modelling remains the only method and effective tool that is used to predict the climate system’s evolution under the influence of natural and anthropogenic perturbations. It is important that mathematics and its methods and approaches have played a vital role in climate research for several decades. In this study, we examined some mathematical methods and approaches, primarily, mathematical modelling and sensitivity analysis, for studying the Earth’s climate system, taking into account the dependence of human health on environmental conditions. The essential features of stochastic climate models and their application for the exploration of climate variability are examined in detail. As an illustrative example, we looked at the application of a low-order energy balance model to study climate variability. The effects of variations in feedbacks and the climate system’s inertia on the power spectrum of global mean surface temperature fluctuations that characterized the distribution of temperature variance over frequencies were estimated using a sensitivity analysis approach. Our confidence in the obtained results was based on the satisfactory agreement between the theoretical power spectrum that was derived from the energy balance model and the power spectrum that was obtained from observations and coupled climate models, including historical runs of the CMIP5 models.