Cadmium (Cd) is a widespread soil contaminant threatening human health. As an energy plant, sorghum (Sorghum bicolor (L.) Moench) has great potential in phytoremediation of Cd-polluted soils. ATP-binding cassette (ABC) transporters perform critical roles in transport of Cd. However, there has not yet been a comprehensive analysis of the ABC gene family in sorghum. In this study, 142 ABC genes in sorghum were identified. Transcriptome study showed 41 SbABCs with differential expression patterns under Cd treatment. Candidate gene-based association study for Cd translocation factors identified five significant SNPs inside the annotated gene SbABCB11. Sequence analysis in different haplotypes demonstrated there were multiple long indel variations in the coding region of SbABCB11. Expression study indicated that SbABCB11-Hap3 was upregulated in roots after Cd treatment. Yeast complementary assay proved that SbABCB11 participated in the efflux of Cd, which was further supported by the localization of SbABCB11 on the plasma membrane. Transient suppression of SbABCB11 via antisense oligodeoxyribonucleotide (asODN) method reduced Cd accumulation in the shoots of sorghum by decreasing the release of Cd into the xylem. Our results provide new insights into the potential roles of SbABCs in sorghum. We revealed that SbABCB11 participated in translocation of Cd from roots to shoots, and there were significant variations in the translocation ability among different haplotypes of SbABCB11. These findings will be of help for the molecular breeding of sorghum germplasms suitable for the phytoremediation of Cd-contaminated soils.