Sub-Saharan Africa concentrates the burden of HIV and the highest adolescent fertility rates. However, there is limited information about the impact of the interaction between adolescence and HIV infection on maternal health in the region. Data collected prospectively from three clinical trials conducted between 2003 and 2014 were analysed to evaluate the association between age, HIV infection, and their interaction, with the risk of maternal morbidity and adverse pregnancy and perinatal outcomes in women from southern Mozambique. Logistic regression and negative binomial models were used. A total of 2352 women were included in the analyses; 31% were adolescents (≤19 years) and 29% HIV-infected women. The effect of age on maternal morbidity and pregnancy and perinatal adverse outcomes was not modified by HIV status. Adolescence was associated with an increased incidence of hospital admissions (IRR 0.55, 95%CI 0.37–0.80 for women 20–24 years; IRR 0.60, 95%CI 0.42–0.85 for women >25 years compared to adolescents; p-value < 0.01) and outpatient visits (IRR 0.86, 95%CI 0.71–1.04; IRR 0.76, 95%CI 0.63–0.92; p-value = 0.02), and an increased likelihood of having a small-for-gestational age newborn (OR 0.50, 95%CI 0.38–0.65; OR 0.43, 95%CI 0.34–0.56; p-value < 0.001), a low birthweight (OR 0.40, 95%CI 0.27–0.59; OR 0.37, 95%CI 0.26–0.53; p-value <0.001) and a premature birth (OR 0.42, 95%CI 0.24–0.72; OR 0.51, 95%CI 0.32–0.82; p-value < 0.01). Adolescence was associated with an increased risk of poor morbidity, pregnancy and perinatal outcomes, irrespective of HIV infection. In addition to provision of a specific maternity care package for this vulnerable group interventions are imperative to prevent adolescent pregnancy.