Abstract Background Postpartum depression (PPD) is considered an important public health problem, and early recognition of PPD in pregnant and lactating women is critical. This study investigated the knowledge, attitude, and practice (KAP) toward PPD among pregnant and lying-in women. Methods This cross-sectional study was conducted at Binzhou Medical University Hospital between September 2022 and November 2022 and included pregnant and lying-in women as study participants. A questionnaire was designed by the researchers that included demographic data and knowledge, attitude, and practice dimensions. Correlations between knowledge, attitude, and practice scores were evaluated by Pearson correlation analysis. Factors associated with practice scores were identified by multivariable logistic regression. Results All participants scored 6.27 ± 2.45, 36.37 ± 4.16, and 38.54 ± 7.93 93 from three sub-dimensions of knowledge, attitudes, and practices regarding PPD, respectively, with statistical differences in the three scores by age, education, and job status (p < 0.05). There were no significant differences between maternal (6.24 ± 2.34, 36.67 ± 3.82 and 38.31 ± 7.27, respectively) and pregnant women (6.30 ± 2.49, 36.00 ± 4.53 and 38.83 ± 8.69, respectively) in the total scores of knowledge, attitude, and practice dimensions. According to the results of multivariate logistic regression, the knowledge (OR = 1.235[1.128–1.353], P < 0.001) and attitude (OR = 1.052[1.005–1.102], P = 0.030) dimension scores were factors influencing the practice dimension scores. Conclusion The KAP of pregnant and lying-in women toward PPD is low. This study suggests that maternal awareness of PPD should be increased through the knowledge and attitudinal dimensions. Preventing PPD in pregnant and lying-in women can be achieved by improving both dimensions, thus enhancing practice.