The U.S. Fish and Wildlife Service listed Anaxyrus canorus, the Yosemite toad, as federally threatened in 2014 based upon reported population declines and vulnerability to global-change factors. A. canorus lives only in California’s central Sierra Nevada at medium to sub-alpine elevations. Lands throughout its range are protected from development, but climate and other global-change factors potentially can limit populations. A. canorus reproduces in ultra-shallow wetlands that typically hydrate seasonally via melting of the winter snowpack. Lesser snowpacks in drier years can render wetland water volumes and hydroperiods insufficient to allow for successful breeding and reproduction. Additionally, breeding and embryogenesis occur very soon after wetlands thaw when overnight temperatures can be below freezing. Diseases, such as chytridiomycosis, which recently decimated regional populations of ranid species, also might cause declines of A. canorus populations. However, reported studies focused on whether climate interacts with any pathogens to affect fitness in A. canorus have been scarce. We investigated effects of these factors on A. canorus near Tioga Pass from 1996 to 2001. We found breeding subpopulations were distributed widely but inconsistently among potentially suitable wetlands and frequently consisted of small numbers of adults. We occasionally observed small but not alarming numbers of dead adults at breeding sites. In contrast, embryo mortality often was notably high, with the majority of embryos dead in some egg masses while mortality among coincidental Pseudacris regilla (Pacific treefrog) embryos in deeper water was lower. After sampling and experimentation, we concluded that freezing killed A. canorus embryos, especially near the tops of egg masses, which enabled Saprolegnia diclina (a water mold [Oomycota]) to infect and then spread through egg masses and kill more embryos, often in conjunction with predatory flatworms (Turbellaria spp.). We also concluded exposure to ultraviolet-B radiation did not play a role. Based upon our assessments of daily minimum temperatures recorded around snow-off during years before and after our field study, the freezing potential we observed at field sites during embryogenesis might have been commonplace beyond the years of our field study. However, interactions among snow quantity, the timing of snow-off, and coincidental air temperatures that determine such freezing potential make projections of future conditions highly uncertain, despite overall warming trends. Our results describe important effects from ongoing threats to the fitness and abundance of A. canorus via reduced reproduction success and demonstrate how climate conditions can exacerbate effects from pathogens to threaten the persistence of amphibian populations.