The coalbed methane (CBM) geology in Guizhou is characterized by a high gas content, pressure and resource abundance, indicating superior CBM resource potential. However, there are also many unfavorable factors, such as complex structure geology, significant regional differences in CBM geology, the widespread development of tectonically deformed coal, and the unclear understanding of the configuration of geological factors for CBM enrichment and high yield, which restrict the increase in CBM production and a large-scale development. Taking the Dahebian Block in Liupanshui coal field and the Dafang Block in Qianbei coal field as examples, this study presented the CBM geological differences between middle- and high-rank coals; their origins were analyzed and the effect of depth on gas content and permeability was discussed. A CBM enrichment and high-yield model was illustrated, and the geologic fitness-related exploration and development methods for Guizhou CBM were finally proposed. The results show that (1) significant differences between the middle- and high-rank coals occur in coal occurrence and distribution, coal qualities, and coal reservoir properties. Compared to Dahebian coal, Dafang coal has a higher coal rank, vitrinite content, and gas content, but a lower number of coal layers and permeability. (2) The sedimentary–tectonic evolution of the Longtan coal-bearing sequence is the fundamental reason for CBM geological differences between the Dadebian Block and Dafang Block, consisting of coal occurrence, qualities, maceral, rank, structure, and their associated reservoir properties. (3) The coordinated variation of gas content and permeability contributes to a greater depth for CBM enrichment and a high yield of the middle-rank coal. It is suggested that the best depths for CBM enrichment and high yield in Guizhou are 600–800 m for the middle-rank coal and 500 m for the high-rank coal, respectively. (4) Considering the bottleneck of inefficient CBM development in Guizhou, we proposed three CBM assessment and development technologies, including the CBM optimization of the classification–hierarchical optimization–analytical hierarchy, multiple coal seams commingling production with the pressure relief of tectonically deformed coal, and surface–underground CBM three-dimensional drainage development. The aim of this study was to provide new insights into the efficient exploration and development of CBM in Guizhou.