The polyphenolic constituents and antioxidant activity of aqueous and acetone extracts of Vachellia karroo leaves were determined in order to evaluate its efficacy in scavenging radicals such as DPPH, ferric reducing power and nitric oxide as an antioxidant model. The flavonols and flavonoid and phenolic content of the leaf extracts were also accessed using benchmark phytochemical reaction methods. Results of the phytochemical analyses revealed the presence of flavonoids and flavonol and phenolic compounds in the leaf extracts. The total phenolic content values in the aqueous and acetone leaf extracts were 7.40 and 11.09 mg tannic acid equivalent/g of extract powder, respectively. The total flavonol and flavonoid content values of the aqueous leaf extracts were 9.90 and 53.23 mg quercetin equivalent/g of extract, respectively, while those of the acetone leaf extracts were 1.18 and 5.18 mg quercetin equivalent/g of extract, respectively. At 0.2 mg/mL, the values for the scavenging activities of the acetone and aqueous extracts of the V. karroo leaves were significantly higher (p < 0.05) than that of the ascorbic acid but comparable to BHT against ferric oxide radicals. The findings from the study reveal that the antioxidative potentials of V. karroo leaf extract and could serve as free radical inhibitors, possibly acting as principal antioxidants.