BackgroundEarly sexual debut is a widely recognized public health issue due to its influence on lifetime multiple sexual partners which can lead to complications such as teenage pregnancy, abortion, HIV/AIDS and other sexually transmitted infections. However, there is paucity of research evidence on sexual behaviour such as age at first sexual intercourse and the number of sexual partnerships among adolescent girls in Ghana. This study aims to examine the influence of age at first sexual intercourse and other determinants on multiple sexual partnerships among adolescent girls aged 15–19 years in Ghana.MethodsData for this study were obtained from the 2022 Ghana Demographic and Health Survey (GDHS) conducted between October 17, 2022 and January 14, 2023. A total weighted sample of 719 sexually active adolescent girls who reported having sexual partners was extracted from the women’s data file. Data were analyzed with SPSS version 27, employing multilevel logistics regression modelling. Statistical significance was set at p < 0.05.ResultsThe average age at sexual debut for adolescent girls aged 15–19 years in Ghana is 15.5 years. A little over half (51.6%) of adolescent girls reported having two or more lifetime sexual partners. Adolescent girls who initiated sex before reaching age 15 were more likely (aOR = 2.00; C.I 1.39–2.87) to have multiple partners compared to those who had their first sex before attaining age 20. After controlling for other factors, girls who had their sexual debut before age 15 had higher odds (aOR = 1.85; C.I:1.30–3.31) of engaging in multiple sexual partnerships. Girls living female headed households (aOR = 2.25; C.I:1.18–4.29] and consuming alcohol (aOR = 2.38; C.I 2.38–1.09–5.17) had higher odds of having multiple sexual partners.ConclusionThe study findings show that early sexual debut, living in female headed household, and consuming alcohol are strong predictors of multiple sexual partnerships among adolescent girls in Ghana. It suggests the need for policies promoting delayed sexual debut and empowering adolescents to make informed decisions to improve sexual health outcomes.