Cropping systems are affected by climate change because of the strong relationship between crop development, growth, yield, CO2 atmospheric concentration and climate conditions. The increasing temperatures and the reduction of available water resources may result in negative impacts on the agricultural activity in Mediterranean environments than other areas. In this study the CERES-Wheat and CROPGRO-Tomato models were used to assess the effects of climate change on winter wheat (Triticum durum L.) and processing tomato (Lycopersicon aesculentum Mill.) in one of most productive areas of Italy, located in the northern part of the Puglia region. In particular we have compared three different General Circulation Models (HadCM3, CCSM3, ECHAM5) subjected to a statistical downscaling under two future IPCC scenarios (B1 and A2). The analysis was carried out at regional scale repeating the simulations for seven homogeneous area characterizing the spatial variability of the region. In the second part of the study, considering only HadCM3 data set, climate change impact on long-term sequences of the two crops combined in three crop rotations were evaluated in terms of yield performances and soil fertility as indicated by the soil organic content of carbon and nitrogen. The comparison between GCMs showed no significant differences for winter durum wheat yield, while noticeable differences were found for yield and irrigation requirements of tomato. Under future scenarios, the production levels were reduced for tomato, whereas positive yield effects were observed for winter durum wheat. For winter durum wheat the simulation indicated that two- and three-year rotations, including one year of tomato cultivation, improved the cereal yield and this positive effect maintained its validity also in future scenarios. For both crops higher requirements of water and nitrogen were predicted under future scenarios. This result coupled with the decrease of yield caused negative reduction of water use efficiency and nitrogen use efficiency for tomato cultivation.