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Diseases characterized by long distance inoculum dispersal (LDD) are among the fastest spreading epidemics in both natural and managed landscapes. Management of such epidemics is extremely challenging because of asymptomatic infection extending at large spatial scales and frequent escape from the newly established disease sources. We compared the efficacy of area‐ and timing‐based disease management strategies in artificially initiated field epidemics of wheat stripe rust and complemented with simulations from an updated version of the spatially explicit model EPIMUL, using model parameters relevant to field epidemics. The model was further used to expand the number of epidemic mitigations beyond that feasible to incorporate in the field. The field experiment was conducted for 2 years in two locations having different climatic conditions. Culling and protection treatments were applied at different times after epidemic initiation and to different spatial extents surrounding the outbreaks. In each experiment, treatments were replicated four times in plots 33.5 m long and 1.52 m wide with a 0.76 × 0.76 m inoculated focus centered within each plot. Disease gradients were assessed along the center lines of the plots at 1.52 m intervals both upwind and downwind from the focus. Both field and simulation results indicated that control measures applied over the entire population were highly effective in suppressing the epidemics by more than 99% but may not always be logistically and economically feasible at large spatial scales. Comparison between the variable sized treatment areas and application timings suggested that implementing contiguous premises (CP) cull at 1 day after first sporulation in the outbreak focus reduced rust by 52% and 60% in Corvallis and Madras, respectively. However, altering the cull size did not significantly affect the disease epidemic development, which suggested that early timing had a greater influence in suppressing the epidemics than did increased area of application. However, sufficiently large, treated areas may compensate for a delay in application timing to some extent. Results from these replicated treatments may help to devise appropriate management strategies for other LDD pathogens. [ABSTRACT FROM AUTHOR]