Vernonia camporum is used ethnomedicinally to treat diseases such as malaria, fever, hypertension, mouth sores, pains, inflammation, and skin rashes in Africa. This study aims at investigating the biological activities (anthelminthic, anti-inflammatory, antioxidant, and antimicrobial) and separating some of the biologically active components in the methanol crude extract of the stem-bark of Vernonia camporum. Phytochemical screening, anthelminthic (Lumbricus terrestris (earthworm)), anti-inflammatory (egg albumin denaturation), antioxidant (DPPH and H2O2 scavenging and total antioxidant capacity (TAC)), and antimicrobial (agar and broth dilution method) assays were performed on the extracts. Column chromatography and FTIR spectroscopic analysis were employed to separate and analyze the least polar constituents of the methanol extract. The preliminary phytochemical analyses revealed the presence of secondary metabolites such as alkaloids, phenols, tannins, saponins, terpenoids, flavonoids, steroids, phytosterols, proteins and amino acids, phlobatannins, glycosides, cardiac glycosides, coumarins, and anthocyanins. The extracts (methanol and hexane) showed a higher concentration-dependent anthelminthic activity. The extracts exhibited high concentration-dependent anti-inflammatory activities with IC50 values of 35.83 ± 3.984 and 53.91 ± 5.8413 µg/mL, respectively. The IC50 values for methanol and hexane extracts in the DPPH assay were 17.70 ± 3.430 and 29.54 ± 1.5437 µg/mL, and those of the H2O2 assay were 243.20 ± 0.1528 and 352.20 ± 12.64 µg/mL, respectively. TAC results for methanol and hexane extracts were recorded as 31.592 ± 1.682 and 30.232 ± 0.445 gAAE/100 g, respectively. The extracts were observed to exhibit antimicrobial activity against test organisms with MICs ranging from 0.1953 to 25.00 mg/mL. Chromatographic separations gave four fractions. FTIR analysis indicated the presence of various functional groups in purified fractions of the methanol extract that confirms the presence of the phytochemicals identified in the screening test. The results indicate that both extracts of V. camporum possess anthelminthic, anti-inflammatory, antioxidant, and antimicrobial activities supporting the traditional usage of this plant.