Ficus sur Forssk (Moraceae) is used in traditional African medicine in the treatment of epilepsy, pain and inflammations. Anticonvulsant activity was investigated using picrotoxin (PTX), strychnine (SCN), isoniazid (INZ), pentylenetetrazole (PTZ) and N-methyl-D-aspartic acid NMDA models of convulsion. The phytochemical analysis of the extract revealed the presence of flavonoids, saponins, tannins, alkaloids and anthraquinone. Oral administration of Ficus sur, 1 h before intraperitoneal injection of chemical convulsants significantly (p < 0.05) delayed the onset and prolonged the duration of convulsions in PTX, SCN, INZ, PTZ and NMDA-induced seizures. However, the anticonvulsant activity of the ethanolic extract of Ficus sur was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist), cyproheptadine (5-HT2 receptor antagonist) and L-NNA (nitric oxide synthase inhibitor) in picrotoxin-induced convulsion. The data obtained suggest that ethanol extract of Ficus sur possessed significant anticonvulsant effect, thereby confirming the traditional uses of Ficus sur in the treatment of epilepsies; mechanisms of which could involve interaction with GABAergic, glycinergic, serotonergic and glutaminergic system barks.