Napoleona vogelii (Lecythidaceae) is used in traditional medicine for the management of pain and inflammatory disorders. This study was conducted to investigate the anti-nociceptive and anti-inflammatory activity of the methanol stem bark extract of N. vogelii in rodents. The extract (100–400 mg/kg) was administered 1 h before intraperitoneal and intraplantar injection of 0.2 mL of 0.6% v/v acetic acid and 0.05 mL of 2% v/v formalin, respectively. Anti-inflammatory activity was investigated using the carrageenan-induced paw edema and formalin-induced arthritis models. Mechanistic studies were conducted by exploring opioidergic, dopaminergic pathways, and inflammatory mediators. There was 62.26% inhibition of inflammatory pain at 400 mg/kg in the formalin-induced paw licking test. In the acetic acid-induced mouse writhing assay, the extract produced a dose-dependent inhibition of writhes with peak effect at 400 mg/kg producing 54.87% inhibition compared with diclofenac at 71.09%. The extract produced 90.98% inhibition of the late phase of carrageenan-induced paw edema and 82.81% inhibition in the formalin-induced arthritis test. The anti-nociceptive activity of the extract was blocked by sulpiride (D2 receptor antagonist; 1 mg/kg) but not by naloxone (opioid receptor antagonist; 5 mg/kg). In addition, pre-treatment of mice with the extract produced 95.08% inhibition of histamine-induced inflammation similar to that of indomethacin at 97.54% and inhibition of serotonin-induced inflammation at 46.79% compared with indomethacin which produced 94.26%. This study demonstrates that the extract possesses anti-nociceptive and anti-inflammatory activity mediated through inhibition of dopaminergic pathways and inflammatory mediators.