Single-cell whole-genome sequencing (WGS) is critical for characterizing dynamic intercellular changes in DNA. Current sample preparation technologies for single-cell WGS are complex, expensive, and suffer from high amplification bias and errors. Here we describe Digital-WGS, a sample preparation platform that streamlines high-performance single-cell WGS with automatic processing based on digital microfluidics. Using the method, we provide high single-cell capture efficiency for any amount and types of cells by a wetted hydrodynamic structure. The digital control of droplets in a closed hydrophobic interface enables the complete removal of exogenous DNA, sufficient cell lysis and lossless amplicons recovery, achieving the low CV and high coverage at multiple scales. The single-cell genomic variations profiling performs the excellent detection of copy number variants (CNVs) with the smallest bin of 150 kb and single-nucleotide variants (SNVs) with alleles drop out (ADO) rate of 5.2%, holding great promise for broader applications of single-cell genomics.