This study examines US productivity growth through the lens of R&D-based growth models. A general R&D-based model, nesting different model varieties, is developed. These varieties are tested using a novel cointegrating relationship and US data for the period 1953–2018. The results provide evidence against the widely used fully endogenous variety and support for other varieties including the semi-endogenous variety. Further, the results are systematically consistent with the presence of fishing-out effects in knowledge production, implying that productivity-enhancing innovations become increasingly harder to achieve as technologies become more advanced. Forecasts suggest that the US productivity growth slowdown continues over the coming decades.