BackgroundCervical cancer is an international public health issue. Nearly all cases of cervical cancer are caused by the human papillomavirus. The HPV vaccine prevents more than 75% of cervical cancer. The extent to which adolescent girls' knowledge and uptake of the HPV vaccine have to be investigated in order to build effective promotion strategies and increase the uptake of the vaccine. The evidence that is currently available in this area is controversial and inconclusive. Hence, this study has estimated the pooled proportion of good knowledge, positive attitude, and uptake of the HPV vaccine and its associated factors among adolescent schoolgirls in Ethiopia.MethodsPubMed, Google Scholar, AJOL, ScienceDirect, and DOAJ were used to search relevant studies. A total of 10 studies were included. The data were extracted by two reviewers using Microsoft Excel and exported to STATA Version 17 for analysis. A random effects model was applied during the analysis. Heterogeneity and publication bias across the studies were evaluated using I2statistics and Egger’s test, respectively. The PROSPERO registration number for the review is CRD42023414030.ResultA total of eight studies comprising 3936 study participants for knowledge and attitude and five studies with 2,481 study participants for uptake of HPV were used to estimate the pooled proportions of good knowledge, a positive attitude, and uptake of the HPV vaccine, respectively. The pooled proportions of good knowledge, positive attitude, and uptake of the HPV vaccine were 55.12%, 45.34%, and 42.05%, respectively. Being an urban resident (OR = 4.17, 95% CI = 1.81, 9.58), having good knowledge (OR = 6.70, 95% CI = 3.43, 13.07), and a positive attitude (OR = 2.04, 95% CI = 1.51, 2.74), were significantly associated with the uptake of the vaccine.ConclusionThe pooled proportions of good knowledge, a positive attitude, and uptake of the HPV vaccine were low in Ethiopia. Being an urban resident and having good knowledge and a positive attitude towards the HPV vaccine were significantly associated with the uptake of the HPV vaccine. We recommend increasing adolescent knowledge, positive attitudes, and uptake of HPV vaccination through school-based seminars, health education, and community mobilization.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12905-023-02412-1.