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Background Hygienic practices during complementary food preparation are suboptimal in developing countries, in Ethiopia in particular. Hygienic complementary food preparation is crucial to prevent childhood communicable diseases like diarrhea and associated malnutrition among children aged 6–24 months. However, in Ethiopia, there is a paucity of evidence on the practice of hygiene during complementary food preparation. Thus, this study is aimed to assess the hygienic practice of complementary food preparation and associated factors among women having children aged 6–24 months in Debark town, northwest Ethiopia. Methods A community-based cross-sectional study was conducted among 423 mothers with 6–24 months of age children from December 1 to January 30, 2021. A simple random sampling technique was used to select the study participants. Data were collected using an interviewer-administered structured questionnaire. Epi-data version 4.6 and SPSS version 23 software were used for data entry and analysis, respectively. Binary logistic regressions (Bivariable and multivariable) were performed to identify statistically significant variables. Adjusted odds ratio with 95% CI was used to declare statistically significant variables on the basis of p-value < 0.05 in the multivariable logistic regression model. Results The study revealed that 44.9% (95% CI (40.2, 49.4%)) of the mothers having children aged 6–24 months had good practice of complementary food preparation. Maternal age of 25–29 years[AOR:3.23, 95% CI: (1.555–9.031)], husband’s attained secondary school and above (AOR:2.65, 95% CI (1.211–5.783)], using modern stove for cooking [AOR:3.33,95% CI (1.404–7.874)], having a separate kitchen[AOR: 8.59, 95%Cl: (2.084–35.376], and having a three bowl dishwashing system(AOR: 8.45, 95% CL: (4.444–16.053)) were significantly associated with good hygiene practice of complementary food preparation. Conclusions The findings have indicated that the majority of the mothers had poor hygienic practices of complementary food preparation. Mother’s age, husband’s educational status, type of stove used for cooking, having a separate kitchen, having a three bowl dishwashing system were factors that significantly influenced the hygiene practice of mothers during complementary food preparation. Therefore, training and counseling mothers and caregivers on complementary food processing and preparation is important and such endeavors which inform the development and implementation of complementary food hygiene interventions in urban communities are recommended.