Background. The overall well-being, sense of stigmatization, and treatment outcome of persons with vitiligo are largely dependent on their social acceptance and this is linked with perception and attitude of this disease in a given population. Therefore, this study assessed the knowledge and attitude of the public towards vitiligo. Methods. A cross-sectional survey was carried out using a self-reported questionnaire distributed to adults living in Mekelle city, Northern Ethiopia from August to November 2019. Individuals who were 18 to 65 years of age and not suffering from vitiligo were included in the study. A self-administered questionnaire that contains a demographic, knowledge, and attitudes parts was used to collect data. Data were entered using Epi Data® version 3.1 and analyzed using SPSS® version 21. Results. Of the total 368 subjects, 300 completed the questionnaires giving 81.5% response rate. The mean age was 30 ± 8.3 years and the male-to-female ratio was 1.14 : 1. Friends or families were reported as the most common source of information (70%) about vitiligo. The overall vitiligo knowledge was sufficient in 68.3% of the participants. Higher vitiligo-related knowledge scores were recorded by people older than 30 and below 50, those of secondary school graduated or more, urban-dwellers, persons who had heard about vitiligo, and persons having families or friends affected by vitiligo. Attitudes towards vitiligo were positive in 43.3% of participants. This was more prevalent among employed persons, those of secondary school graduated or more, and persons having families or friends affected by vitiligo. Moreover, sufficient knowledge was significantly related to positive attitudes towards the disease (p<0.0001). Conclusion. Even though the majority of the respondents had sufficient knowledge, we still found misconceptions and negative attitudes towards vitiligo. Therefore, it is still crucial to educate the public about vitiligo to ultimately improve the well-being of patients with vitiligo.