Crop-pasture rotations (CP) have been proposed as a more sustainable management system than continuous cropping (CC) under Uruguayan conditions. However, the impact of crop-pasture rotations under conventional tillage (CT) and no-till systems (NT) has not been evaluated in terms of long-term inputs and economic viability. We conducted a 12-y field study on a clay loam (Typic Argiudol), located in western Uruguay, to determine inputs (agrochemicals, equipment operation costs), gross margin, and net returns. Under CC (averaged over 12-y) net crop return was 19% higher for NT than CT (U$395 and U$340 ha^-1 y^-1, respectively). An increase in yields without variation in costs explained the higher net returns with NT. Operation costs were not significantly different between tillage systems, but NT increased the use of agrochemicals (glyphosate and nitrogen use) and reduced equipment operation costs (principally fuel). Within CT, the use of CP increased net crop returns 14% compared with CC (U$340 and U$386 ha^-1 y^-1 for CC and CP, respectively), but the inclusion of pastures did not affect net crop return under NT systems (422 ha^-1 y^-1 and 395 ha^-1 y^-1 for CP and CC, respectively). CT under CC presented the lowest net return compared with the other three alternatives. Net return from livestock production averaged U$323 ha^-1 y^-1. Our study indicated that crop-pasture rotations maintain or increase crop productivity, reducing inputs and protecting soil resources in Uruguay.