Cane dieback and foliar necrosis caused by an unknown pathogen were observed in elderberry (Sambucus nigra subspecies) plantings in early Spring 2016. Studies were conducted to identify the causal organism and determine the effects of infection on vegetative growth and fruiting of selected elderberry cultivars under controlled conditions. A Heterophoma sp. was isolated from symptomatic ‘Ranch’ elderberry canes growing in a commercial planting in Missouri. In the subsequent 2017 experiments, all canes of ‘Bob Gordon’ plants inoculated with this Heterophoma isolate had reduced cane lengths, reduced numbers of leaves and leaflets, and failed to produce fruit. In a study using ‘Scotia’, none of the 32 inoculated canes had symptomatic tissue; but in a subsequent study, one of 16 inoculated canes had slight cane dieback, indicating a potential difference in cultivar susceptibility to the pathogen. In 2018, seven elderberry cultivars (‘Adams II’, ‘Bob Gordon’, ‘Marge’, ‘Ozark’, ‘Scotia’, ‘Wyldewood’, and ‘York’) were inoculated with the same Heterophoma isolate, which was subsequently reisolated from the boundary of symptomatic and asymptomatic tissue, thereby confirming pathogenicity of the fungus. The fungus was tentatively identified as H. novae-verbascicola (Aveskamp, Gruyter & Verkley) Q. Chen & L. Cai based on analysis of genomic DNA from the internal transcribed space (ITS) region. Only two of 16 ‘Scotia’ inoculated canes had cane dieback in 2018, whereas inoculated canes of all other cultivars developed symptoms. Cane and foliar growth of each inoculated cultivar was less than the associated noninoculated control at 14, 30, and 60 days after treatment (DAT). Among inoculated symptomatic plants, ‘Marge’ canes produced more vegetative growth than all other cultivars, and ‘Adams II’, ‘Ozark’, and ‘York’ canes generally produced the fewest number of leaves and leaflets at 60 DAT. Flowering was observed on canes of noninoculated control plants, but not on inoculated symptomatic canes by 60 DAT. Thus, the newly reported cane dieback disease of elderberry, caused by Heterophoma sp., adversely affected plant growth and fruiting of Sambucus nigra subspecies. However, ‘Scotia’ elderberry plants were less susceptible to the fungal infection than other cultivars, indicating that it may be possible to use ‘Scotia’ to develop new elderberry cultivars with improved resistance to infection by Heterophoma.