A novel sorghum variety designated XS4321 and seed, plants, plant parts and plant cells thereof are produced from a cross of inbred sorghum varieties. Methods for producing a sorghum plant comprise crossing hybrid sorghum variety XS4321 with another sorghum plant. Sorghum variety XS4321, the seed, the plant produced from the seed, and variants, mutants, and minor modifications of sorghum variety XS4321 are provided. Methods for producing a sorghum plant containing in its genetic material one or more traits introgressed into sorghum variety XS4321 include one or both of backcross conversion and transformation of one or both inbred parents. The sorghum seed, plants and plant parts produced thereby are described.