The BraTS 2021 challenge celebrates its 10th anniversary and is jointly organized by the Radiological Society of North America (RSNA), the American Society of Neuroradiology (ASNR), and the Medical Image Computing and Computer Assisted Interventions (MICCAI) society. Since its inception, BraTS has been focusing on being a common benchmarking venue for brain glioma segmentation algorithms, with well-curated multi-institutional multi-parametric magnetic resonance imaging (mpMRI) data. Gliomas are the most common primary malignancies of the central nervous system, with varying degrees of aggressiveness and prognosis. The RSNA-ASNR-MICCAI BraTS 2021 challenge targets the evaluation of computational algorithms assessing the same tumor compartmentalization, as well as the underlying tumor's molecular characterization, in pre-operative baseline mpMRI data from 2,040 patients. Specifically, the two tasks that BraTS 2021 focuses on are: a) the segmentation of the histologically distinct brain tumor sub-regions, and b) the classification of the tumor's O-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. The performance evaluation of all participating algorithms in BraTS 2021 will be conducted through the Sage Bionetworks Synapse platform (Task 1) and Kaggle (Task 2), concluding in distributing to the top ranked participants monetary awards of $60,000 collectively.