A major geological risk factor for engineering and energy-related applications, such as CO2 storage and unconventional hydrocarbon production, is the geomechanical integrity of mudrocks. The goal of this work is to better constrain the macroscopic mechanical properties resulting from microstructural components by investigating the effects of thermal maturity, mineral composition, diagenesis and organic richness on the mechanical properties of Cretaceous mudstones in two surface sections (San Vicente de Chucurí and La Cristalina Creek) and one well (La Luna-1) from the Middle Magdalena Valley Basin (MMVB), Colombia. The thermal maturity of 22 rock samples was evaluated via organic source-rock screening and determination of illite crystallinity (Reichweite). Both geothermometers placed the La Luna Formation rock samples from San Vicente de Chucurí and the La Luna-1 well within the oil generation window (80°C–120 °C). In contrast, the rock samples of the Guaguaquí Group from La Cristalina Creek in the southern part of the basin are within the gas window (>180 °C). The mineralogy of organic-rich mudstones in the MMVB is dominated by quartz and calcite. Moreover, mudstones from the MMVB have a wide range of organic richness and clay contents, with organic abundances comparable to and clay contents lower than those found in other source-rock reservoirs. The Young's modulus (EIT), Martens hardness (HM), and creep (CIT), as determined through microindentation experiments, highly varied, but overall, the findings suggest that the Cretaceous rocks of the MMVB present conditions favorable for hydraulic fracturing. Furthermore, the viscoelastic properties of Cretaceous rocks in the MMVB are influenced primarily by the concentrations of strong minerals (quartz and calcite) and weak components (clay and TOC). Specifically, an increase in the concentration of weak components compared with that of strong minerals leads to an increase in CIT and a decrease in HM and EIT, and vice versa. Unlike other source-rock reservoirs, there are no indications of a strong correlation between thermal maturity and mechanical properties, suggesting a decoupling of these parameters in rocks of the MMVB. A close scanning electron microscopy examination of the rocks indicated that the observed weak to moderate correlation between thermal maturity and mechanical properties appears to result from rock silicification and calcite cementation caused by the precipitation of these minerals at early stages of diagenesis. This observation implies that the impact of diagenesis on rock geomechanics of silica-rich and calcareous-rich mudstones may override or be more important than the effects of thermal maturity, which, along with clay and organic matter contents, are the greatest controls in the geomechanics of argillaceous source-rock reservoirs.