Objective The aim of this study was to investigate the existence, knowledge, and the attitude of female students towards premenstrual syndrome (PMS). Methods This cross-sectional study was conducted in three universities in Karachi, Pakistan. A total of 448 female students participated in the study. The clinical criterion of American College of Obstetricians and Gynecologists (ACOG) for PMS was used to assess the prevalence of PMS in the participants. The questionnaire was set in four parts, one each to assess the knowledge, the attitude, and practices regarding PMS and one to assess the gap between self-perceived PMS and actual PMS. Data were analyzed descriptively using the Statistical Package for the Social Sciences (SPSS), version 20 (IBM SPSS Statistics, Armonk, NY). Results The majority (96.4%) of female students were aware of PMS, while only 19% females knew about premenstrual dysphoric disorder. The self-reported prevalence of PMS was 79.5% and the prevalence using the ACOG criteria was 23.9%. Common symptoms were irritability, angry outbursts, depression, breast tenderness, and gastrointestinal problems. More than half (60.4%) of the participants reported PMS disturbed their normal routine, while 81.5% reported stress exacerbated their symptoms. The majority (77.5%) of women believed PMS was a significant issue to be discussed but 49.4% did not take treatment for their PMS. Conclusion There is a significant impact of PMS in the lives of Pakistani women, and it is a common problem all over the globe. Despite the growing awareness, there remains a considerable deficiency of knowledge about the necessity to consult a doctor or seek treatment for their symptoms.