A 2-year conservation agriculture experiment was conducted in Southern Italy on durum wheat continuous cropping. Aim of the research was to assess the durum wheat productivity and grain quality in reduced soil tillage systems, according to conservation agriculture principles. The interactions among experimental treatments and climate revealed a close relationship among grain yield, grain quality and wheat growth conditions. Specifically, conventional tillage (CT, plowing and 2 disc harrowing) showed in the 2-year period higher grain production than reduced tillage treatments, minimum (MT, 1 disc harrowing) and No tillage (NT), especially for good crop water availability (3.29 t ha–1 of grain yield in CT, 2.67 in MT and 2.54 in NT). The amount of rainfall (above the average in both years) and its distribution in the growing seasons (more regular in the first year) strongly influenced wheat-grain quality indices (11.97% of protein content in the first year and 9.82% in the second one). Also, the wheat quality resulted more sensitive to the “Year × Tillage” interaction, with differences among tillages more evident in the second year and favourable to NT and MT. Spectral vegetation indexes (NDVI and TVI) measurements at flowering, have been shown to be useful to support farmers in N-late application for improving grain wheat quality. From this experiment carried out during the conversion period and in wet years, wheat managed with CT resulted in higher grain yield and quality, while only test weight showed a significant “Year × Tillage” interaction. Further indications emerged on the need to supply additional (10–20%) seed amount at sowing and crop nitrogen fertilizer in the first transition years in reduced tillage systems compared to conventional ones.