Recombination is an essential process in bacterial drug resistance evolution. Fluoroquinolones, an important class of antibiotics, have been reported to stimulate recombination in Escherichia coli. Bacteria’s sublethal exposure to several other antibiotics from different families, including strong inducers of the SOS stress response and antimicrobial peptides, does not affect recombination rates. Here we ask why fluoroquinolones, and no other antimicrobials, increase recombination rates. We found that the fluoroquinolone ciprofloxacin stimulated recombination in E. coli not only via increased SOS induction but also by DNA double-strand breaks (DSBs). On this basis, we tested whether other antimicrobials, known for their ability to cause double-strand breaks, such as mitomycin C and bleomycin, also affect recombination rates. Indeed, both antibiotics also increased recombination frequency. We found a positive correlation between the number of DNA double-strand breaks and the recombination frequency. These results imply that recombination, at least in Gram-negative bacteria, is conservative, and even if the substrate of recombination is available, the basal recombination rate is low, and it is more intended to repair than to generate diversity. We also show that only antibiotics that cause DNA double-strand breaks can increase genetic diversity via recombination and increase the risk for antibiotic resistance.