The ability to use blood to predict the outcomes of Parkinson’s disease, including disease progression and cognitive and motor complications, would be of significant clinical value. We undertook bulk RNA sequencing from the caudate and putamen of postmortem Parkinson’s disease (n= 35) and control (n= 40) striatum, and compared molecular profiles with clinical features and bulk RNA sequencing data obtained from antemortem peripheral blood. Cognitive and motor complications of Parkinson’s disease were associated with molecular changes in the caudate (stress response) and putamen (endothelial pathways) respectively. Later and earlier-onset Parkinson’s disease were molecularly distinct, and disease duration was associated with changes in caudate (oligodendrocyte development) and putamen (cellular senescence), respectively. Transcriptome patterns in the postmortem Parkinson’s disease brain were also evident in antemortem peripheral blood, and correlated with clinical features of the disease. Together, these findings identify molecular signatures in Parkinson’s disease patients’ brain and blood of potential pathophysiologic and prognostic importance.