Background Although the rate of childhood acute lymphoblastic leukemia (ALL) is increasing in Africa, there is a dearth of information on the disease and the dynamics of hemostatic parameters with therapy. Methods In this case-control study, we evaluated variations in the level/activity of selected coagulation parameters among cALL in Ghana and healthy controls stratified by stage of therapeutic management. Results In all, the research recruited 104 participants comprising 26 cALL cases and 78 healthy controls. The cALL group had significantly higher prothrombin time (PT) (p = 0.001), activated partial thromboplastin time (APTT) (p < 0.0001) and D-dimers (p = 0.001) but lower platelet (PLT) count, protein C (PC) (p < 0.0001), protein S (PS) (p < 0.0001) and antithrombin III (ATIII) (p < 0.0001) compared to controls. Compared to the healthy controls, activity of PC was lower during induction (p < 0.0001), consolidation (p = 0.005) and maintenance phases of chemotherapy (p = 0.012) while activities of PS and ATIII were lower at both induction (p < 0.0001, p = 0.006) and consolidation (p < 0.0001, p = 0.018) phases of chemotherapy. Conclusion Our findings provide evidence in the context of Africa and corroborates previous reports that cALL could result in a state of hypercoagulability, possibly leading to a high risk of thrombosis and thromboembolic complications. This possibly increased risk is not limited to the induction phase but also the consolidation phase.