Background Exploring the association of coronavirus-2019 disease MESHD (COVID-19) mortality with chronic pre-existing conditions may promote the importance of targeting these populations during this pandemic to optimize survival. The objective of this systematic review and meta-analysis is to explore the association of pre-existing conditions with COVID-19 mortality. Methods We searched MEDLINE, OVID databases, SCOPUS, and medrxiv.org for the period December 1, 2019, to May 1, 2020. The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing conditions. Comorbidities explored were cardiovascular diseases MESHD ( coronary artery disease MESHD, hypertension MESHD hypertension HP, cardiac arrhythmias MESHD arrhythmias HP, and congestive heart failure HP heart failure MESHD), chronic obstructive pulmonary disease MESHD chronic obstructive pulmonary disease HP, type 2 diabetes, cancer, chronic kidney disease HP kidney disease MESHD, chronic liver disease MESHD, and stroke MESHD stroke HP. Two independent reviewers extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified. Results Ten chronic conditions from 19 studies were included in the meta-analysis (n = 61,455 patients with COVID-19; mean age TRANS, 61 years; 57% male TRANS). Overall the between-study study heterogeneity was medium and studies had low publication bias and high quality. Coronary heart disease MESHD, hypertension MESHD hypertension HP, congestive heart failure HP heart failure MESHD, and cancer significantly increased the risk of mortality from COVID-19. The risk of mortality from COVID-19 in patients with coronary heart disease MESHD was 2.4 times as high as those without coronary heart disease MESHD (RR= 2.40, 95%CI=1.71-3.37, n=5) and twice as high in patients with hypertension MESHD hypertension HP as high as that compared to those without hypertension MESHD hypertension HP (RR=1.89, 95%CI= 1.58-2.27, n=9). Patients with cancer also were at twice the risk of mortality from COVID-19 compared to those without cancer (RR=1.93 95%CI 1.15-3.24, n=4), and those with congestive heart failure HP heart failure MESHD were at 2.5 times the risk of mortality compared to those without congestive heart failure HP heart failure MESHD (RR=2.66, 95%CI 1.58-4.48, n=3). Conclusions COVID-19 patients with all any cardiovascular disease MESHD, coronary heart disease MESHD, hypertension MESHD hypertension HP, congestive heart failure HP heart failure MESHD, and cancer have an increased risk of mortality. Tailored infection MESHD prevention and treatment strategies targeting this high-risk population are warranted to optimize survival.