Sweet potato exhibits a prostrate growth habit, which makes weed management to be manually performed or conducted through the application of selective herbicides. Considering the absence of registered herbicides for the selective control of broad leaf weeds on the sweet potato crop, we investigated the physiological and agronomic responses of the sweet potato cultivar Duda, selected for its great potential in biofuel production, to different post-emergence herbicides. Two experiments, one conducted under field conditions and the other under controlled (potted plants) conditions, were performed under a randomized complete block design, with four replicates each. Four different herbicides, atrazine and S-metolachlor (3,5 L.ha-1), carfentrazone-ethyl (0,75 L.ha-1), fomesafen and fluazifop-P-butyl (1,8 L.ha-1) and nicosulfuron (1,25 L.ha-1), were used and the experiments were composed by five treatments with the control (no herbicide application) treatment,. Physiological indicators, including carbon assimilation, stomatal conductance, leaf transpiration rate, internal CO2 concentration, and water-use efficiency were monitored at 24 h, 48 h and 15 d after herbicides application, while agronomic evaluations were performed at 30 and 152 days from herbicide application. Application of atrazine (inhibitor of photosystem II) together with S-metolachlor (inhibitor of cell division/elongation) led to reductions on the physiological indices soon after treatment imposition but it had no effect on dry matter accumulation in the shoot, nor on the roots, not affecting the starch content, storage root productivity, and estimated ethanol production as well. In contrast, application of carfentrazone-ethyl, a protoporphyrinogen oxidase inhibitor, exerted significant negative physiological and agronomic effects, decreasing root productivity and estimated ethanol yield. We conclude that the use of atrazine in a mixture with S-metolachlor represents a suitable selective approach for the control of broad leaf weeds in sweet potato crops.