The deformation and failure characteristics of rock caused by periodic changes of temperature are not only significantly different from that under normal temperature, but also significantly different from that produced by a single high-temperature event. Here, using a three-dimensional digital image correlation (3D-DIC) integrated test system, mechanical and micro-damage tests of red sandstone are performed under cycles of high-temperature and natural-cooling with a temperature range of 25°C to 300°C and the number of cycles varying between 0 and 25. Macroscopic, mesoscopic and microscopic characteristics such as rock strength, deformation, strain field and fracture morphology are examined and their evolution with the number of heating-cooling cycles is discussed. Using the time-history evolution of the differentiation rate of the precursor anomaly (En), the characteristic coefficient (K) and the damage variable (DF), three kinds of characteristic time points are put forward to quantify the incubation and development time of precursor abnormal characteristics and are used to divide the whole process of deformation and failure. These time points are the precursor abnormal differentiation time (PADT) tE, the precursor abnormal startup time (PAST) tK, and the precursor abnormal failure time (PAFT) tD. Test results show that: (1) The action of cyclic high-temperature natural-cooling not only shows the strengthening effect of temperature, but also shows the strengthening effect of a certain number of cycles. (2) The evolution sequence of the three precursor abnormal characteristic moments is PADT, PAST and PAFT in turn, and this sequence can intuitively describe the whole complex process of rock deformation and failure, and there are wave peaks in the evolution curve with the number of high-temperature cycle. (3) The effect of high temperature (i.e., 300°C) cyclic heating on rock properties is similar to the threshold effect of a single high-temperature heating event.