Coronavirus disease 2019 (COVID-19) is an infectious disease that traces its earliest known cases to the Hubei region of China in late 2019. As the COVID-19 pandemic has spread across the globe wreaking unprecedented disruption, increasing levels of xenophobia and racial discrimination have been documented against those of Asian descent. We investigate the historical connections between disease and rise of xenophobia as described in the peer-reviewed literature addressing prior epidemics, such as Ebola and the Hong Kong Flu, in conjunction with concurrent cases of prejudice toward certain groups of people. Attempts to better understand why such attitudes emerge are examined in the context of xenophobic actions during pandemics. Prevailing views suggest that xenophobia ultimately leads to increased stigmatization of those afflicted by disease, which in turn leads to decreased trust in the medical system, resulting in a negative feedback loop. Accurate disseminated information and improved public education on sources and modes of transmission of infectious diseases are essential to check xenophobic tendencies, reduce negative effects and foster greater cooperation.