In 2009, the United States experienced a record drop in its tuberculosis (TB) case rate, coinciding with a major economic downturn. To investigate this relationship, we modeled short-term changes in gross domestic product, unemployment, and immigration as predictors of TB incidence. We also correlated each state's 2009-2010 change in unemployment with its 2008-2009 change in TB incidence. Although economic factors did not explain the decline, the 2009-2010 change in unemployment negatively correlated with incidence. We hypothesize that factors related to increased unemployment, such as diagnostic delay, may have played a role in the sudden drop in TB case rates.