Streams are integrative systems spanning multiple spatial and temporal scales. Stream researchers, land-use managers, and policy decision makers must consider the downstream displacement of streams when approaching questions about stream ecosystems. The study of how anthropogenic land-use influences streams demands an ecosystem perspective, and this dissertation is an example of applying large scale analyses of stream reach responses, and linking the activity of humans in the landscape to stream structure and function. I investigate whether rural development and agriculture land-cover types influence abiotic and biotic stream responses. I establish a method for considering land-cover as an independent variable at multiple scales throughout a streams' watershed using hydraulic modeling. The travel time required for water to drain from the watershed to a stream reach provided a continuous index to delimit watershed sub portions along a spatial continuum. Within travel time zones (TTZs), I consider land-use at increasingly larger scales relative to a stream reach within which biotic responses are typically measured. By partitioning land-cover in TTZs, I was able to determine the spatial scale at which land-cover was most likely to influence in-stream responses. I quantified a suite of physical and biotic responses typical to the aquatic ecology literature, and found that streams did not respond much to rural development. Rural development influenced suspended and depositional sediments, and likely altered watershed hydrology though I was unable to find significant evidence supporting a hydrologic effect. Subtle differences in assemblages suggest that differences in sediment dynamics influenced macroinvertebrates and fish. Using the Land Cover Cascade (LCC) design, I link the influence of land-cover to biotic responses through a suite of multivariate models, focusing on sediment dynamics in an attempt to capture the subtle influence of hydrology and sediment dynamics. My dissertation provides future researchers with improved methods for considering land-cover as an independent variable, as well as introduces multivariate models that link land-cover to sediment dynamics and biota. My dissertation will assist future research projects in identifying specific mechanisms associated with stream responses to disturbance.