This study was carried out to investigate the in vitro antimicrobial properties of crude methanolic extract of Chromolaena odorata and its interactions with some standard antibiotics (ofloxacin, ciprofloxacin, and gentamicin) on Pseudomonas aeruginosa isolated from wound samples. P. aeruginosa was isolated from wound samples from hospital patients in Enugu State, Nigeria, using standard bacteriological methods. Methanolic extraction of C. odorata was carried out using Soxhlet extractor. The antimicrobial activity and in vitro interactions were evaluated using a combination of agar well diffusion and broth dilution techniques. The findings of this study showed that all the P. aeruginosa isolates were susceptible to the C. odorata methanolic crude extract at high concentrations. There was an enhancement of the potency of the methanolic crude extract when combined with low concentrations of standard antibiotics compared to its potency when tested alone. Our findings give credence to the folkloric use of C. odorata for the treatment of wounds, especially P. aeruginosa-infected wounds. There could be beneficial clinical application of the coadministration of standard antibiotics and the crude extract of C. odorata in the treatment of wound infections caused by P. aeruginosa.