Key message <p>Twenty-seven favorable teosinte alleles reducing cadmium accumulation or enhancing tolerance were identified across 44 QTLs, and three promising candidate genes for the <i>qCCA3-3</i> locus were further screened through integrated RNA-seq and qRT-PCR.</p> <p>Cadmium (Cd) contamination in agricultural soils poses serious threats to food security and human health through crop bioaccumulation. This study integrated quantitative trait locus (QTL) mapping in a large maize–teosinte BC₂S₃ recombinant inbred line population (866 lines genotyped with 19,838 single nucleotide polymorphism markers) with transcriptome profiling to dissect the genetic basis of Cd accumulation and tolerance in maize seedlings. A total of 44 QTLs distributed across all ten chromosomes were identified, each explaining 1.4–6.6% of phenotypic variance, with predominantly additive gene action (59% of QTLs). Notably, 27 favorable alleles derived from the wild progenitor teosinte (<i>Zea mays</i> ssp. <i>parviglumis</i>) were found to reduce Cd accumulation or enhance tolerance, demonstrating that maize wild relatives harbor valuable genetic diversity for stress adaptation. Near-isogenic lines validation confirmed that the teosinte allele at the <i>qCCA3-3</i> locus simultaneously reduces Cd accumulation and enhances tolerance under Cd stress. Transcriptome integration prioritized 19 candidate genes for <i>qCCA3-3</i>, including a glutathione S-transferase (<i>Zm00001d043344</i>) and two WRKY transcription factors (<i>Zm00001d043062</i> and <i>Zm00001d043063</i>). These findings provide validated QTL, elite genetic stocks, and candidate genes as practical resources for developing Cd-safe maize cultivars through marker-assisted and genomic selection strategies.</p>