The giant reed, Arundo donax, is a perennial grass species that has become an invasive plant in many countries. Expansive stands of A. donax have significant negative impacts on available water resources and efforts are underway to identify biological control agents against this species. The giant reed grows under adverse environmental conditions, displaying insensitivity to drought stress, flooding, heavy metals, salinity and herbaceous competition, thus hampering control programs. To establish a foundational molecular dataset, we used an llumina Hi-Seq protocol to sequence the transcriptome of actively growing shoots from an invasive genotype collected along the Rio Grande River, bordering Texas and Mexico. We report the assembly of 27,491 high confidence transcripts (≥200 bp) with at least 70% coverage of known genes in other Poaceae species. Of these 13,080 (47.58%), 6165 (22.43%) and 8246 (30.0%) transcripts have sequence similarity to known, domain-containing and conserved hypothetical proteins, respectively. We also report 75,590 low confidence transcripts supported by both trans-ABBySS and Velvet-Oases de novo assembly pipelines. Within the low confidence subset of transcripts we identified partial hits to known (19,021; 25.16%), domain-containing (7093; 9.38%) and conserved hypothetical (16,647; 22.02%) proteins. Additionally 32,829 (43.43%) transcripts encode putative hypothetical proteins unique to A. donax. Functional annotation resulted in 5,550 and 6,070 transcripts with assigned Gene Ontology and KEGG pathway information, respectively. The most abundant KEGG pathways are spliceosome, ribosome, ubiquitin mediated proteolysis, plant–pathogen interaction, RNA degradation and oxidative phosphorylation metabolic pathway. Furthermore, we also found 12, 9, and 4 transcripts annotated as stress-related, heat stress, and water stress proteins, respectively. It is envisaged that these resources will promote and facilitate studies of the abiotic stress capabilities of this exotic plant species, which facilitates its invasive capacity. Supplemental Excel data files with the article detail functional annotation of Arundo donax high confidence and low confidence genes. Data are also available at https://www.ncbi.nlm.nih.gov/nuccore/GBRH01000000 . The assembled and annotated A. donax USA genotype Rio Grande RNA transcriptome has been deposited at DDBJ/EMBL/GenBank under the project accession PRJNA256910.