Basil downy mildew, caused by the pathogen Peronospora belbahrii, is a major problem for sweet basil growers worldwide. The genome sequences of both Ocimum basilicum and P. belbahrii were recently completed but extensive transcriptome analysis of this pathosystem has not been completed. RNA sequencing was performed using basil leaf samples (of a susceptible cultivar) collected three and six days after inoculation with sporangia from an Illinois isolate of P. belbahrii and 11,890 differentially expressed basil genes were identified (q value <0.05). Gene enrichment analysis identified several Gene Ontology (GO) terms that were upregulated in inoculated basil leaves compared to mock control leaves which included groups of putative defensive genes (False Discovery Rate (FDR) < 0.05). In addition, there were several GO terms related to photosynthesis in the infected leaves that were downregulated in comparison to control leaves at statistically significant levels (FDR < 0.05). The pathogen's transcriptome data also identified three highly expressed transcripts encoding secreted glycoside hydrolases (GH, each transcript level was greater than 70,000 transcripts per million, TPM), which likely release sugars from the plant cell walls needed for the growth of the pathogen. Moreover, two of these GH transcripts were also highly expressed (greater than 30,000 TPM) in susceptible basil leaves infected by a Hawaiian isolate of P. belbahrii in an independent experiment performed with a different basil cultivar. These results demonstrate a multilevel response of sweet basil to P. belbahrii that is not effective enough to block the pathogen.