Americans’ perceptions of science are structured by overlapping cultural fields of politics and religion, and those cultural fields vary over time in how they influence opinion about science. This paper provides a historical narrative for understanding how religious and political factors influence public perceptions of science over the last four decades. Using data from the 1974–2012 General Social Survey, the impact of religious and political factors are examined and compared across decades using heterogeneous ordinal logistic regression models and ordinal structural equation models. Estimates show that the impact of sectarian Protestant identification and fundamentalist beliefs in the Bible are increasingly linked to lower levels of confidence in science, and that these religious factors also influence the impact of political conservatism and Republican Party identification. Political conservatism has become more oppositional towards science, and Republicans have become less enthusiastic compared to periods when science was primarily linked to militaristic endeavors.