Wheat head blast (WHB), caused by the fungus Magnaporthe oryzae Triticum (MoT) is a major concern in South America and in South Asia. To date, the 2NS translocation is the only useful source of resistance to WHB effective against MoT prevalent races. Our objective was to identify non-2NS sources of resistance to WHB among elite cultivars, breeding lines, and wild-relative accessions. Over 780 accessions were evaluated under field and greenhouse conditions in Brazil and Bolivia and in biosafety level-3 laboratories in the U.S. The MoT isolates B-71 (2012), 008 (2015), and 16MoT001 (2016) were used for controlled experiments, while isolate 008 was used for field experiments. A wheat differential set was used to characterize the aggressiveness of the isolates. Resistant and susceptible checks were included at all experiments. Four spring wheat CIMMYT breeding lines (CM22, CM49, CM52, and CM61) and four wheat wild-relatives, Ae. tauschii (10142, 1624, 1667, and 10140) were identified as resistant (<5% of severity) or moderately resistant (5% severity <25%) to WHB. Experiments conducted at the seedling stage showed little correlation with disease severity at the head stage. MoT isolate 16MoT001 was significantly more aggressive against 2NS-based varieties. The low frequency of WHB resistance and the increase in aggressiveness of newer MoT isolates highlight the threat that the disease poses to wheat production worldwide and the urgent need to identify and deploy novel sources of resistance.