Background For more than 150 years, war surgery has been at the heart of the humanitarian assistance offered by the International Committee of the Red Cross (ICRC) in conflict zones around the world. Mental health and psychosocial support (MHPSS) is increasingly recognized as an integral part of the medical care offered to this highly vulnerable group of patients. This study seeks to identify patient characteristics associated with high distress prior to MHPSS and predictors of improvement following it. Methods Between October 2018 and April 2020, 2,008 weapon-wounded patients received MHPSS in ICRC-supported hospitals in the Democratic Republic of Congo (DRC), Mali and Nigeria. The 21-item Depression and Anxiety Scale (DASS21), the Impact of Events Scale Revised (IES-R) and the ICRC functionality scale for Africa were administered before and after the MHPSS response. Logistic regression models were used to measure associations between outcome and exposure variables. Data was initially collected for monitoring purposes and analyzed retrospectively for the sake of this study. Results The main reasons for surgery were firearms (65%), other weapons (13%) and mines (5%). Linear trends were found between increasing number of days between violence and first consultation and decreased likelihood of presenting high levels of anxiety (aOR 0.75, p = 0.014), and stress (aOR 0.78, p = 0.032). Violence committed by military/armed group was associated with increased likelihood of reporting high levels of anxiety (aOR 2.47, p = 0.047). On the IES-R, high scores at baseline were more likely to be found among illiterate patients (aOR 0.08, p = 0.042) and having been wounded by firearms considerably increased the likelihood of reporting high levels of PTSD (aOR 21.34, p = 0.035). Following MHPSS, 92.28% of the patients showed a reduction in symptoms on the DASS21, 93.00% showed a reduction in symptoms on the IES-R and 83.04% showed an improvement on the ICRC Africa functioning scale. On the DASS21, factors negatively associated with improved anxiety included lack of social support (aOR 0.17, p = 0.047) and suffering from a chronic medical/physical condition (aOR 0.40, p = 0.013). Patients with reduced IES-R scores were more likely to have a high level of education (aOR 8.95, p = 0.029) and to have received MHPSS that lasted between 22 and 30 days (aOR 8.73, p = 0.008). Predictors of improved functioning included being 35–44 years of age (aOR 3.74, p = 0.004) and suffering from a severe or chronic medical condition (aOR 1.66, p = 0.044). Conclusions Clinical implications of this study include the increased involvement of family and other caregivers in the MHPSS and longer-term follow-up of patients with severe and/or chronic medical conditions. Further research is needed with regard to joint psychological and physical outcomes, the role of the patient’s education level and the personal styles and techniques used by the counsellors.