Background/Aims Danger signs are indicators of complications easily recognised by non-clinical personnel that may occur during pregnancy, childbirth or in the postpartum period. Some maternal deaths can be attributed to a lack of information about postnatal danger signs. Most studies on knowledge of danger signs have investigated groups of participants with mixed parities, meaning there is limited research on knowledge among first-time mothers. The aim of this study was to determine first-time mothers’ knowledge of postnatal danger signs and associated factors in Uganda. Methods This was a cross-sectional study that recruited 358 primigravidas. Data on knowledge of postnatal danger signs and the participants’ obstetric and sociodemographic factors were collected through interviewer-administered questionnaires. A multivariable logistic regression model was used to determine factors associated with knowledge of postnatal danger signs. Results Of the 358 participants, 63.4% could name at least one postnatal danger sign. Factors associated with knowledge of postnatal danger signs were having secondary or tertiary education (P=0.002), attending more than four antenatal care visits (P<0.001) and having access to information platforms (P<0.001). Conclusions There is insufficient knowledge of postnatal danger signs among first-time mothers at Tororo General Hospital. First-time mothers require health education as they lack experience and knowledge of danger signs. The use of media sources to convey health information should be strengthened in the healthcare system.