Plant invasion may have significant ecological and socio-economic impacts across agroecologies. Chromolaena odorata (Asteraceae) is one of the world’s most invasive plants albeit it is considered a suitable fallow plant in West Africa. However, its impacts on soil biological processes are poorly understood. This study was conducted in intermingled forest and savanna sites invaded by C. odorata in Central Côte d’Ivoire (West Africa) to bridge this knowledge gap. Invaded forest sites (COFOR) were compared to adjacent natural forest fragments (FOR) while invaded savanna sites (COSAV) were compared to adjacent natural savanna fragments (SAV). Soil (0–10 cm depth) physico-chemical variables, including soil organic C (SOC), total soil N and available N and P concentrations were measured. Additionally, soil microbial biomass (MBC), carbon mineralization (Cmin), acid phosphatase, β-glucosidase, and fluorescein diacetate were measured. Further, the MBC/SOC ratio and the metabolic quotient (qCO2) were calculated. An index of invasion effect (IE) computed as the cumulative percent change in the microbial and enzyme activities was determined for each ecosystem context. Results showed that soil MBC and MBC/SOC ratio declined in COFOR relative to FOR. In general, Cmin, enzymatic activities, qCO2 and available N and P significantly increased in the C. odorata sites relative to the respective reference ecosystems, particularly savanna, potentially due to a larger gap in the litters’ quality. As a result, the invasion effect was twice as high in savanna (IE = 292.8%) as in forest (IE = 147.5%). However, a Principal Component Analysis showed that the COSAV were close to COFOR stands without mixing, probably due to contrasting initial soil organic matter and clay contents. These results improved our knowledge on the changes in soil microbial attributes and the mechanisms of soil fertility restoration or improvement in response to C. odorata invasion in natural forests and savannas of West Africa.