Introduction Breast cancer is the most common type of cancer among women, particularly in low and middle-income countries. Breast self-examination is one of the non-invasive methods of screening in which a woman looks at her breast for any abnormal findings like lumps, distortions, or swellings. Despite, realized effects of breast self-examination in detecting breast cancer earlier, the vast majority of the cases still present with an advanced stage. Objective This study aimed to assess knowledge, attitude, and practices toward breast self-examination and associated factors among women in Gondar Town, Northwest Ethiopia, 2021. Methods A community-based cross-sectional study was conducted on women living in Gondar town. A simple random sampling method was used to select 571 participants. Interviewer administered questionnaires were used for data collection. Data was entered into Epi-data version 4.6 and exported to Statistical Package for Social Science (SPSS) version 25 for analysis. Multivariate logistic regression was used where a p-value < 0.05 was used to identify variables significantly associated with the outcome variable. Result From the total of 571 women, about 541 participants were involved in the study with a response rate of 94.7%. Of these, 56%, 46% and 45.8% of women had adequate knowledge, favourable attitudes, and performed breast self-examination (BSE) respectively. Women College and above AOR: 3.8 (95% CI: 1.43–10.14) and spouses College and above AOR: 3.03 (95% CI: 1.04–8.84), Women College and above AOR: 4.18 (95% CI: 1.59–10.92) and history of breast cancer AOR: 6.06 (95% CI: 2.19–16.74) and knowledge level AOR: 2.67 (95% CI: 1.18–6.04) were significantly associated with knowledge, attitudes, and practices towards breast self-examination respectively. Conclusion The findings of this study were considerable for inadequate knowledge, unfavourable attitude and poor practice towards BSE among women. Emphasis should be made on boosting the knowledge, attitude, and practice of the women toward breast self-examination and strengthening the implementation of comprehensive, systematic, and continuous BSE educational programs that were recommended along with a breast cancer awareness campaign.