There is no effective way to detect structure variations (SVs) and extra-chromosomal circular DNAs (ecDNAs) at single-cell whole-genome level. We developed a novel third-generation sequencing platform-based single-cell whole-genome sequencing (scWGS) method named SMOOTH-seq (single-molecule real-time sequencing of long fragments amplified through transposon insertion). We evaluated the method for detecting CNVs, SVs, and SNVs in human cancer cell lines and a colorectal cancer sample and showed that SMOOTH-seq reliably and effectively detects SVs and ecDNAs in individual cells, but shows relatively limited accuracy in detection of CNVs and SNVs. SMOOTH-seq opens a new chapter in scWGS as it generates high fidelity reads of kilobases long.