Developmental epileptic encephalopathy (DEE) comprises neurodevelopmental disorders with early-onset seizures and developmental impairment. Despite >900 implicated genes, many patients remain undiagnosed after short-read sequencing (SRS). We assessed long-read genome sequencing (LR-GS) in 38 previously unsolved infantile-onset DEE probands (10 singletons, 28 trios). Variant detection included single nucleotide variants (SNVs), structural variants, copy number variants and short tandem repeats in established repeat expansion disease genes. LR-GS identified candidate variants in 8 out of 38 probands (21%) missed by SRS: five large deletions, one SNV in a low-mappability region of NSF, one case resolved via haplotype phasing of compound heterozygous SNVs without parental samples and one case where LR-GS detected an allele missed due to coverage gaps. An additional eight probands (21%) harboured variants technically detectable by SRS but were missed due to newly associated genes, synonymous variants lacking splicing evaluation or prior analytic pipelines. LR-GS substantially increases diagnostic yield in unsolved infantile-onset DEE, supporting its incorporation into clinical workflows as a second-tier genetic test for otherwise unsolved neurodevelopmental disorders.