Conformal growth of atomic-thick semiconductor layers on patterned substrates can boost up the performance of electronic and optoelectronic devices remarkably. However, conformal growth is a very challenging technological task, since the control of the growth processes requires utmost precision. Herein, we report on conformal growth and characterization of monolayer MoS2 on planar, microrugged, and nanorugged SiO2/Si substrates via metal-organic chemical vapor deposition. The continuous and conformal nature of monolayer MoS2 on the rugged surface was verified by high-resolution transmission electron microscopy. Strain effects were examined by photoluminescence (PL) and Raman spectroscopy. Interestingly, the photoresponsivity (∼254.5 mA/W) of as-grown MoS2 on the nanorugged substrate was 59 times larger than that of the planar sample (4.3 mA/W) under a small applied bias of 0.1 V. This value is record high when compared with all previous MoS2-based photocurrent generation under low or zero bias. Such enhancement in the photoresponsivity arises from a large active area for light-matter interaction and local strain for PL quenching, wherein the latter effect is the key factor and unique in the conformally grown monolayer on the nanorugged surface. © Copyright 2018 American Chemical Society.