The aim of the study was to examine the differences in the chemical composition, polyphenol compounds, antioxidant activity, and in vitro rumen fermentation among six varieties of sorghum stalks. The results show that maoliangnuo 1 (M1) contained a higher (p < 0.05) level of dry matter, and jinzhong 405 (J4) contained a higher (p < 0.05) level of crude protein content. The concentrations of neutral detergent fiber, acid detergent fiber, and cellulose were significantly higher (p < 0.05) in stalk jinliangnuo (JN). The levels of chlorogenic acid, homoorientin, isovitexin, vitexin, rhoifolin, genistin, quercetin, apigenin, aloe emodin, emodin, and total polyphenols were all significantly (p < 0.05) higher in maohongnuo 6 (M6) than in the other stalks. Moreover, stalk M6 contained higher (p < 0.05) levels of total antioxidant capacity (TAC), glutathione peroxidase (GPX), catalase (CAT), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging capacity. There were significant (p < 0.05) positive correlations between total polyphenols and TAC, superoxide dismutase, GPX, CAT, and DPPH free-radical scavenging capacity. The total gas production was significantly (p < 0.05) influenced by the sorghum stalk variety and incubation time. Stalk J4 displayed higher values for the (p < 0.05) immediately soluble fraction and the potential extent of gas production, while stalk M6 exhibited a significantly lower (p < 0.05) insoluble fraction level. Furthermore, stalk M6 exhibited a significantly higher level of (p < 0.05) ruminal fluid propionic acid, but its level of butyric acid and its ratio of acetic acid to propionic acid were both significantly lower (p < 0.05). Taken together, the results reported in this paper indicate that the chemical composition, polyphenol compounds, antioxidant activity, and in vitro rumen fermentation all vary greatly among different varieties of sorghum stalks.