Paleoproterozoic igneous suites across the West African Craton have previously been classified as Tonalite-Trondhjemite-Granodiorite (TTG)-like, and in many cases this association has been used as a line of evidence to associate the tectonic evolution of the region with Archean-style vertical accretion tectonics. More recently, these felsic intrusions have been classified to have evolved from calc-alkaline to more potassic granitic rocks. The present study builds upon recent geochronological and isotopic studies by presenting a geochemical characterization of granitic rocks from the Baoulé-Mossi domain, particularly from Burkina Faso, southern Mali and eastern Guinea, during the 2250–2000 Ma period. The studied samples were classified to be predominately magnesian, alkali-calcic to calc-alkalic and metaluminous to peraluminous. The described characterization is similar to the main portion of Cordillera batholiths or inboard from the mentioned type batholiths or with plutons derived from over-thickened crust equivalent to S and I type pluton granites. A small portion of the studied samples were found to be predominately ferroan and alkali-calcic to calc-alkalic, which are commonly associated with A type granites. Trace element characteristics suggest that the studied rocks originated from heterogeneous magmas which are characterized by REE anomalies consistent with an arc type system that was subject to crustal shortening and thickening. Spatio-temporal characterization of the geochemical data presented as part of this study shows that magmatism evolved from east to west and from older to younger. Eastern samples are predominately older (>ca. 2100 Ma), in general are more sodic and present (La/Yb)N ratios that are equivalent to the ratios present in Archean TTGs. Younger samples (<ca. 2100 Ma) which are predominately concentrated in the western portion of the study area are more potassic. These geochemical differences from east to west support the notion that the Baoulé-Mossi domain is the result of the amalgamation of at least two crustal blocks. These blocks are interpreted to have been indented by the Archean Kenema-Man domain after ca. 2100 Ma, as suggested by a change in the Na2O/K2O ratio that indicates an evolution from magmatic accretion/crustal growth to crustal reworking.