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Background Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals. Methods Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson’s chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20–34 years. Results A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06–1.23), low birth weight (aOR: 1.46; CI 1.34–1.59), and early neonatal deaths (aOR: 1.58; CI 1.23–2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02–1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12–9.13) compared to mothers 20–34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7–14.3) was statistically significant when compared to mothers 20–34 years (1.6 per 10,000 births; 95% CI 0.9–2.6). Conclusions This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population., Plain English Summary Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals. All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes. Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20–34 years). Adolescent mothers were more likely than mothers (20–34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20–34 years). In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions.