Background Cervical cancer is a malignant tumor of the lower-most part of the uterus and major cause of morbidity and mortality among women's in the world. Its high mortality rate in the globe can be reduced through comprehensive approaches' that include; primary prevention, early diagnosis, effective screening, and treatment packages. This study was aimed to assess the knowledge and practice of cervical cancer screening and its associated factors among reproductive age group women in districts of Gurage zone, Southern Ethiopia, 2019. Methods A community-based cross-sectional study design was conducted from March 1-30, 2019. A total of 268 respondents were selected using a systematic sampling technique. Data was collected using pretested, semi-structured, and interviewer-administered questionnaires. Data were entered into Epi data version 3.1software and exported to SPSS 24 for analysis. Bivariate and multivariate analyses with a 95% confidence level was done and variables (P <0.05) were deemed statistically significant. Result A total of 260 respondents participated in the study with a response rate of 97%. About 3.8% of the respondents had experiences cervical cancer screening and 26.2% of respondents had good knowledge. Early age at first sex [AOR = 6.05 (95%CI; 1.167-31.36)], having information about cervical cancer [(AOR = 10.2 (95% CI 1.9-96.4)], and multiple sexual partners [AOR = 3.96 (95%