C2H2 zinc finger protein (C2H2-ZFP) is one of the most important transcription factor families in higher plants. In this study, a total of 145 C2H2-ZFPs was identified in Sorghum bicolor and randomly distributed on 10 chromosomes. Based on the phylogenetic tree, these zinc finger gene family members were divided into 11 clades, and the gene structure and motif composition of SbC2H2-ZFPs in the same clade were similar. SbC2H2-ZFP members located in the same clade contained similar intron/exon and motif patterns. Thirty-three tandem duplicated SbC2H2-ZFPs and 24 pairs of segmental duplicated genes were identified. Moreover, synteny analysis showed that sorghum had more collinear regions with monocotyledonous plants such as maize and rice than did dicotyledons such as soybean and Arabidopsis. Furthermore, we used quantitative RT-PCR (qRT-PCR) to analyze the expression of C2H2-ZFPs in different organs and demonstrated that the genes responded to cold and drought. For example, Sobic.008G088842 might be activated by cold but is inhibited in drought in the stems and leaves. This work not only revealed an important expanded C2H2-ZFP gene family in Sorghum bicolor but also provides a research basis for determining the role of C2H2-ZFPs in sorghum development and abiotic stress resistance.