Humans have substantially altered global carbon (C), nitrogen (N), phosphorus (P), and hydrologic cycles. These alterations are negatively impacting ecosystem structure and function, particularly in aquatic ecosystems. Climate and land-use change are also affecting stream thermal regimes and vegetation cover, potentially affecting resource availability. Forest headwater streams make up the majority of river network cumulative length, are pivotal in the processing of nutrients and organic matter, and vulnerable to nutrient pollution and climate-driven changes in discharge and temperature. In this dissertation I use both observational and experimental approaches to assess how nutrients and variation in climate versus basal resources affect detritus-based headwater streams. Using an ecosystem-scale nutrient-enrichment experiment, I quantified how N and P concentrations affected basal resource quantity and stoichiometry and subsequent ecosystem-level nutrient retention in organic matter. I found that nutrient storage capacity declined with enrichment in forest streams due to the rapid depletion of detrital carbon, despite increases in mass-specific nutrient content of detritus. Standing stocks of N and P in leaf litter were rapidly depleted, which was not balanced by increases in algal standing stocks. Algal biofilm biomass was co-limited by N and P concentration and light availability. Biofilm stoichiometry was driven largely by stream water P. Using a long-term, observational dataset, I quantified how variation in discharge, temperature, and organic matter resources affects community structure of a forest stream invertebrate community. I found that the magnitude of community turnover differed between two habitat types. Climate-related variables had larger effects than organic matter on community composition. In contrast, organic matter quantity had a greater effect on community biomass than climate-variables in one but not both habitats. This dissertation highlights the value of both ecosystem-level experimental manipulations and long-term observational studies to make ecologically important inferences to help guide management and restoration of headwater stream ecosystems. Collectively, my results provide insights into how major global-change drivers are affecting headwater forest stream organic matter resources and invertebrate communities.