A unique foliar disease of spinach, determined to be caused by Pythium aphanidermatum, was observed on spinach in Yuma County, AZ and Imperial County, CA desert spinach production areas in both 2015 and 2016. The foliar symptoms of the disease included water-soaked foliage, rapid collapse of young plants, and white, aerial, cottony mycelia. The disease was associated with hot (27 to 42°C) and wet conditions associated with overhead irrigation under high-density plantings (>8.0 million seeds/ha). Isolations were performed on symptomatic tissue, and DNA was recovered from pure culture of the isolates recovered and sequenced using the internal transcribed spacer (ITS) ribosomal DNA (rDNA) primers ITS1/ITS4 and gene cytochrome oxidase I (COXI) primers FM55 and FM59. BLAST searches in GenBank indicated that the isolates were P. aphanidermatum based on 99 to 100% homology of ITS rDNA. Moreover, the DNA sequences of the ITS and COXI were identical for the five representative isolates. The objective of this research was to determine whether P. aphanidermatum recovered from symptomatic spinach tissue was able to cause foliar web blight and damping-off of spinach and other crops. In addition to spinach, other hosts evaluated included cotton, soybean, pepper, tomato, cucumber, melon, squash, lettuce, corn, wheat, and rice in greenhouse trials. Inoculations were performed by either foliar inoculations or infesting the soil with plugs of potato dextrose agar colonized by the P. aphanidermatum. Web blight symptoms were severe on spinach and all other dicotyledonous hosts tested, except lettuce. No web blight symptoms were observed on corn or rice, and only minor symptoms were observed on 10-day-old seedlings of wheat. P. aphanidermatum caused severe preemergence damping-off of all dicotyledonous plant species tested but only caused limited seedling size reduction in corn and wheat. Mefenoxam treatment of spinach seed provided complete protection against preemergence damping-off of spinach at both low (0.15 g a.i./kg of seed) and high (0.70 g a.i./kg of seed) rates of application, and the high rate of the application resulted in complete protection against web blight of spinach for 10 to 20 days after planting.