Fire blight, caused by the bacteria Erwinia amylovora, is one of the most important diseases of apples. Despite over 200 years of intense investigation, it continues to cause devastating losses to growers worldwide. The most effective management tool in the Eastern US is the antibiotic streptomycin. However, antibiotic use in agriculture has come under scrutiny and there is a need to better understand the sustainability of streptomycin and alternative management solutions. The first goal of this research was to investigate impacts of streptomycin and alternatives on fire blight disease management and orchard health. Application of the plant growth regulator prohexadione-calcium pre-bloom was investigated as a novel alternative to antibiotics. Results indicated significant reduction in disease incidence to levels comparable with streptomycin, without compromising tree growth. Separate work investigated effects of streptomycin on endophytic bacterial communities in the canopy, communities potentially implicated in orchard health and antibiotic resistance. Minimal effects were detected on abundance and structure of communities, indicating the sustainability of current streptomycin programs. The second goal of this work was to describe distribution and spread of fire blight at multiple scales, with consideration for streptomycin resistance. First, we investigated risk of fire blight development and spread using mechanical thinning and pruning. Field trials indicated both practices could be used safely, and any risk mitigated by applying streptomycin after mechanical treatment. Next, distribution within orchard blocks was described for two fields over two years using spatial analyses. These case studies illustrated different mechanisms of introduction and spread. Finally, we investigated geographic distribution of E. amylovora strains and streptomycin resistance in apple production regions in the Northeastern US. Over 150 isolates were described in terms of streptomycin resistance phenotype and CRISPR profile. Several CRISPR profiles were widely distributed, while many others were only identified in one location. In a streptomycin resistant E. amylovora outbreak in Wayne County, all isolates exhibited CRISPR profiles matching the original SmR isolates discovered in NY, indicating the outbreak likely resulted from imperfect eradication. The work presented herein will inform recommendations for sustainable fire blight management, with immediate impacts to commercial production in NY State and beyond.