Drought stress is detrimental to male reproduction in maize (Zea mays L.), largely through reducing the quantity and quality of pollen grains. However, transcriptional response of maize pollen grains to drought stress has not been well documented. We compared pollen gene expression for a maize hybrid (ZhongDan909) under well-watered and drought-stress conditions, based on RNA-Seq validated by quantitative real-time PCR analysis. Expression of 6424 genes and 1302 transcripts was altered in pollen grains of maize subjected to 7 days of drought during flowering. Gene Ontology annotations showed 308 differentially expressed genes, annotated and classified into 50 primary functional categories. Kyoto Encyclopedia of Genes and Genomes analyses revealed 44 differentially expressed genes in nine metabolic pathways. In relation to carbohydrate metabolism pathways, there was downregulation of a polygalacturonase gene, which could reduce cell wall lysis in early pollen germination, and an increase in callose synthase transcripts along with reduced cellulase transcripts. These altered gene expressions responsible for cell wall integrity may inhibit the initiation of pollen tube growth. The onset of tube growth could be further impeded by observed changes in gene expression that potentially influence hormone metabolism (including downregulation of AUXIN RESPONSE FACTOR 18 and EIN3-BINDING F-BOX), reduce mitochondrial function, and alter protein translation. Genes with potential roles in adaptation were also altered in their transcript levels. These included genes encoding the upregulated transcription factor ZmNF-YC2, and the downregulated ZmbHLH13, a negative regulator of jasmonic acid responses. The upregulated flavin enzyme gene DIHYDROLIPOYL DEHYDROGENASE 1, associated with increased levels of reactive oxygen species, is of interest in relating redox homeostasis to stress adaptation. Overall, the analyses identified a suite of genes involved in the development of pollen grains and tubes and responsive to drought stress. The findings enhance understanding of the gene networks underlying compromised pollen viability under drought stress.