Many Caribbean coral reefs are near collapse due to various threats. An emerging threat, stony coral tissue loss disease (SCTLD), is spreading across the Western Atlantic and Caribbean. Data from the U.S. Virgin Islands reveal how SCTLD spread has reduced the abundance of susceptible coral and crustose coralline algae and increased cyanobacteria, fire coral, and macroalgae. A Caribbean-wide structural equation model demonstrates versatility in reef fish and associations with rugosity independent of live coral. Model projections suggest that some reef fishes will decline due to SCTLD, with the largest changes on reefs that lose the most susceptible corals and rugosity. Mapping these projected declines in space indicates how the indirect effects of SCTLD range from undetectable to devastating.