The cereal disease Fusarium crown rot (FCR), caused by the fungal pathogen Fusarium pseudograminearum (Fp), is a major constraint to cereal production worldwide. Nitrogen (N) fertilizer is estimated to be approximately 30% of the input costs for grain growers in Australia and is the primary driver of yield and grain protein levels. When targeting high yield and protein, generous nitrogen fertilizer applications are thought to result in large biomass production, which exacerbates FCR severity, reducing grain yield and quality. This research was undertaken to investigate the effect of temporal N availability in high-protein bread and durum wheat varieties on FCR severity. Laboratory and controlled environment experiments assessed the relationship between FCR and N at a mechanistic and plant level. An in vitro study demonstrated an increase in Fp mycelial growth under increased N availability, especially when N was supplied as urea compared with ammonium nitrate. Similarly, under controlled environmental conditions, increased soil N availability promoted FCR severity within infected plants. Stem N transfer efficiency was significantly decreased under FCR infection in both bread and durum wheat varieties by 4.5% and 10.2%, respectively. This new research demonstrates that FCR not only decreases yield and grain quality but appears to have previously unrecognised detrimental impacts on nitrogen-use efficiency in wheat. This indicates that the current impact of losses from FCR may also decrease N-use inefficiencies, as well as yield and quality penalties. An improved understanding of the interactions and restrictions of FCR infection may allow growers to better manage the disease through manipulation of the soil’s temporal N availability.