We study the photoresponse of single-layer MoS2 field-effect transistors by scanning photocurrent microscopy. We find that, unlike in many other semiconductors, the photocurrent generation in single-layer MoS2 is dominated by the photothermoelectric effect and not by the separation of photoexcited electron–hole pairs across the Schottky barriers at the MoS2/electrode interfaces. We observe a large value for the Seebeck coefficient for single-layer MoS2 that by an external electric field can be tuned between −4 × 102 and −1 × 105 μV K–1. This large and tunable Seebeck coefficient of the single-layer MoS2 paves the way to new applications of this material such as on-chip thermopower generation and waste thermal energy harvesting.