The mechanistic and therapeutic differences in the cellular response to DNA damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we examined the effects of 12 DNA damaging agents on the complete pool of ~4700 nonessential, barcoded homozygous diploid deletion strains of Saccharomyces cerevisiae. In our protocol, a pool of barcoded homozygous deletion strains is grown competitively in the presence of compound. Individual strain abundance is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. Extrapolation of the resulting signal intensities allows determination of the relative sensitivity of each strain in the pool. These screens identified genes involved in well characterized DNA damage response pathways including nucleotide excision repair, homologous recombination repair, and cell cycle checkpoint control. We also uncovered genes whose role in the DNA damage response was not previously established. Each compound produced a unique genome-wide profile, both with respect to the magnitude of strain sensitivity and to the temporal response of different deletion strains to different treatment. Analysis of these data allowed us to determine the relative importance of DNA repair modules for resistance to each of the 12 profiled compounds. Comparing and clustering the data for 12 distinct compounds uncovered both known and potentially novel functional interactions that comprise the DNA damage response.