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Objectives Preconception care can have a major public health impact by reducing maternal and childhood mortality and morbidity. Despite this importance, preconception care is still not implemented in majority of developing countries. Therefore, this study aimed to assess the proportion of knowledge of preconception care and its associated factors among reproductive-age women in Debre Berhan Town, Ethiopia.Design and methods A community-based, cross-sectional study was employed from 1 March to 30 March 2019 among reproductive-age women. Data were collected via a face-to-face, interviewer-administered questionnaire. Data were entered into EpiData V.4.6 and exported to SPSS V.25 for analysis. In a multivariable logistic regression analysis, variables with p<0.05 were declared statistically significant. The strength of statistical association was measured using adjusted OR (AOR) and 95% CI.Setting and participants The study was conducted in Debre Berhan Town, Ethiopia. A total of 414 reproductive-age women were enrolled in the study.Outcome Knowledge of preconception (good or poor).Results Of the total 414 participants, 71 (17.1%) had good knowledge about preconception care. Women’s occupation (AOR: 8.68, 95% CI 1.25 to 60.3), monthly income (AOR: 9.89, 95% CI 1.93 to 50.76), gravidity (AOR: 0.28, 95% CI 0.14 to 0.58), contraceptive use (AOR: 4.95, 95% CI 1.09 to 22.39), history of congenital abnormality (AOR: 7.53, 95% CI 2.03 to 27.96), history of neonatal death (AOR: 6.51, 95% CI 1.62 to 26.18) and time to reach a health facility (AOR: 0.37, 95% CI 0.17 to 0.79) were statistically associated with knowledge about preconception care.Conclusions In this study area, only less than one-fifth of reproductive-age women had good knowledge of preconception care. Therefore, to improve women’s knowledge about preconception care, a strong collaborative effort including several sectors should be made.