We present long-term growth trends for 13 freshwater mussel species from two unregulated rivers and one regulated river in the southeastern U.S. Coastal Plain. We also collected baldcypress (Taxodium distichum (L.) Rich.) tree cores adjacent to mussel collection sites in one river and directly compared tree and mussel chronologies in this river. To extend our analysis spatially, we examined published baldcypress chronologies from six other unregulated rivers throughout the region. Biochronologies were developed using standard dendrochronology techniques and we explored relationships between annual growth and a suite of streamflow variables in each river. Growth of mussels in unregulated rivers was negatively correlated with annual flood pulse count and May and June discharge, but positively correlated with annual low pulse count and annual number of hydrographic reversals. Baldcypress growth in unregulated rivers was positively correlated with May and June discharge and negatively correlated with annual low pulse count. Mussel growth in the regulated river was not correlated with any streamflow variable suggesting that biological rhythms are decoupled from hydrologic variations in this system. This study shows how interannual variability in streamflow can benefit diverse taxa in floodplain rivers over long periods and how river regulation can disrupt these relationships.