Stroke is the second leading cause of death and the third leading cause of long-term disability in the world. Despite much effort in the past to explore the genetic relationships of stroke and associated factors, underlying genetic risk mechanisms are still incompletely understood. Recognising this gap, this study aimed to explore the novel putative causal genetic relationships of various complex traits with stroke leveraging genetic data. We used data from genome-wide association studies (GWAS) and employed statistical genetics methods to identify potential causal relationships between stroke and 1,504 complex traits of the UK biobank. We found that 262 traits were genetically correlated with stroke risk (false discovery rate, FDR <0.05). Of those correlated traits, 14 showed robust evidence for genetic causality. These causal traits include major conditions, including cardiovascular disorders, metabolic and health-related conditions, liver enzyme, and blood markers, recapitulating previously identified associations, and revealing novel discoveries linking these traits with stroke risk. Subsequently, gene-based tests and functional enrichment analyses revealed key biomarkers and underlying biological processes between those causal traits and stroke. Our findings suggest the diverse genetic factors and biological mechanisms contributing to stroke risk. These insights offer promising targets for addressing the causal traits, which could inform future preventive strategies for stroke management.