Because the meta-instability stage before an earthquake can be found in rock-deformation experiments in the laboratory, great expectations are placed on the detection of possible precursors in earthquake forecasting and prediction. However, varietal observations are difficult to compare, and it is very difficult to distinguish to which stage the observed value belongs. The top priority is to study the relationship between the observations and the meta-instability stage in a uniform system of measurement. The 2014 Ludian M6.5 earthquake, which occurred in the southeastern region of the Qinghai-Tibet Plateau, was surrounded by 122 observatories for groundwater, electromagnetism, and surface deformation within a 300-km radius. Many data were observed before and after the Ludian earthquake, which provided a great case to study the relationship between the observations, stress evolutions, and meta-instability stage before the earthquake. We determined the detailed spatiotemporal variations in groundwater temperature, water level, chemical ion measurement, and crust deformation by strain meter and tilt meter. Following the previous study on the relationship between the observations and stress field, we simply classified all these data from 78 observatories into three groups: stress increased, stress disturbed, and uninfluenced. The results show that the stress field displayed a four-quadrant pattern around the seismogenic structure of the 2014 Ludian earthquake, which is called the Baogunao-Xiaohe Fault and is known as a buried branch fault of the Daliangshan fault. Along with the orientation of fault-block movement, the stress decreased at the back while increasing at the front. In addition, some stress perturbations were found along nearby large active faults, such as the Xianshuihe-Anninghe-Zemuhe-Xiaojiang fault zone, which is a deep-cutting active fault belt confining the Sichuan-Yunnan block. Based on the spatiotemporal evolution of the stress field and distribution of aftershocks, we simplified the seismogenic structure to a set of conjugated strike–slip faults. The nonlinear friction finite-element method was applied to simulate the stress variations before and after the extensive disengagement and slip of nodes on the fault plane. The computed stress field is consistent with the observed phenomenon and the meta-instability stage could be distinguished out from our simulation. Our research can be used to help detach earthquake precursors and determine whether the earthquake system is in the meta-instability stage.