The Infinium DNA Methylation BeadChips have significantly contributed to population-scale epigenetics research by enabling epigenome-wide trait association discoveries. Here, we design, describe, and experimentally verify a new iteration of this technology, the Methylation Screening Array (MSA), to focus on human trait screening and discovery. This array utilizes extensive data from previous Infinium platform-based epigenome-wide association studies (EWAS). It incorporates knowledge from the latest single-cell and cell type-resolution whole genome methylome profiles. The MSA is engineered to achieve scalable screening of epigenetics-trait association in an ultra-high sample throughput. Our design encompassed diverse human trait associations, including those with genetic, cellular, environmental, and demographical variables and human diseases such as genetic, neurodegenerative, cardiovascular, infectious, and immune diseases. We comprehensively evaluated this array's reproducibility, accuracy, and capacity for cell-type deconvolution and supporting 5-hydroxymethylation profiling in diverse human tissues. Our first atlas data using this platform uncovered the complex chromatin and tissue contexts of DNA modification variations and genetic variants linked to human phenotypes.Informatics for MSA data preprocessing and functional analysis is available in the R/Bioconductor package SeSAMe (version 3.22+): https://bioconductor.org/packages/release/bioc/html/sesame.html The complete MSA manifest, design criteria, technical, human trait, and functional annotations are available at https://zwdzwd.github.io/InfiniumAnnotation The generated human cell line, primary tissue methylome profiles (N=420), and EM-seq data are available in the Gene Expression Omnibus with accession GSE264438 and GSE267407.