The composition of diamond‐hosted inclusions provides insight into the character of the sub‐cratonic lithosphere of the Guiana Shield. Guyana's Paleoproterozoic diamonds preserve an inclusion suite comprised of forsterite (Fo ∼89.3–91.8), enstatite, chromite, and Cr‐pyrope. Raman thermobarometry of entrapped olivine and pyrope inclusions indicate entrapment pressures of ∼5.3–7.0 GPa. Unpolarized Fourier transform infrared spectroscopic measurements of forsterite and enstatite inclusions produce low absorbances from OH. Using established calibrations, those absorbances indicate forsterite and enstatite contain median values of 26 ± 14 and 14 ± 18 ppm H2O, respectively, and suggest a high effective viscosity of 1023.7 ± 2.1 Pa∙s for the lithospheric mantle. When combined with inclusion thermobarometry, diamond residence temperatures suggest paleo‐geotherms ranging from 35 to 40 mW m−2. Low‐to‐moderate Fe2O3 content (1.9 ± 0.8 wt.%) and low oxygen fugacity (log ƒO2 (ΔFMQ) −1.6 ± 1.1) determined from chromite inclusions indicate crystallization in reducing conditions. Forsterite and chromite inclusions retain evidence for metasomatic alteration, including Mn‐enrichment in forsterite and chromite rich in Zn. These characteristics indicate that the sub‐cratonic lithosphere of the Guiana Shield experienced episodes of partial melting and fluid‐driven metasomatism of dry, strongly viscous, and moderately depleted garnet‐spinel harzburgite. The Guiana Shield has been relatively stable since the Paleoproterozoic, meaning diamond inclusions may also provide the best means for understanding current conditions in the region's lithospheric mantle.