High-resolution large-eddy simulation (LES) is exploited to study indoor air turbulence and its effect on the dispersion of respiratory virus-laden aerosols and subsequent transmission risks. The LES modeling is carried out with unprecedented accuracy and subsequent analysis with novel mathematical robustness. To substantiate the physical relevance of the LES model under realistic ventilation conditions, a set of experimental aerosol concentration measurements are carried out, and their results are used to successfully validate the LES model results. The obtained LES dispersion results are subjected to pathogen exposure and infection probability analysis in accordance with the Wells–Riley model, which is here mathematically extended to rely on LES-based space- and time-dependent concentration fields. The methodology is applied to assess two dissimilar approaches to reduce transmission risks: a strategy to augment the indoor ventilation capacity with portable air purifiers and a strategy to utilize partitioning by exploiting portable space dividers. The LES results show that use of air purifiers leads to greater reduction in absolute risks compared to the analytical Wells–Riley model, which fails to predict the original risk level. However, the two models do agree on the relative risk reduction. The spatial partitioning strategy is demonstrated to have an undesirable effect when employed without other measures, but may yield desirable outcomes with targeted air purifier units. The study highlights the importance of employing accurate indoor turbulence modeling when evaluating different risk-reduction strategies.