Efforts to monitor coral reefs rarely combine ecological and genetic tools to provide insight into the processes driving patterns of change. We focused on a coral reef at 14 m depth in St. John, US Virgin Islands, and used both sets of tools to examine 12 colonies of Orbicella (formerly Montastraea) annularis in 2 photoquadrats that were monitored for 16 yr and sampled genetically at the start and end of the study. Coral cover and colony growth were assessed annually, microsatellites were used to genetically identify coral hosts in 2010, and their Symbiodinium were genotyped using chloroplastic 23S (cloning) and nuclear ITS2 (cloning and pyrosequencing) in 1994 and 2010. Coral cover declined from 40 to 28% between 1994 and 2010, and 3 of the 12 sampled colonies increased in size, while 9 decreased in size. The relative abundance of Symbiodinium clades varied among corals over time, and patterns of change differed between photoquadrats but not among host genotypes. Symbiodinium communities in 8 corals in 1 photoquadrat differed among colonies and changed over time, with a trend towards reduced abundance of clade C and increased abundance of clade B. Symbiodinium communities in 4 corals in the second photoquadrat were similar among colonies, dominated by clade C, and remained relatively constant in clade composition over time. Based on an analysis that sampled only a small number of corals, but is unique in the long temporal scale and the combination of techniques employed, this study demonstrates that the processes underlying shifts in coral cover are complex and difficult to predict. Meter-scale variation in reef microhabitats affected Symbiodinium communities in O. annularis, and host genotype coupled with variation in Symbiodinium communities appeared to mediate colony success.