This study was carried out to determine the co-occurrence of deoxynivalenol (DON) and the sum of T2 and HT2 toxins in durum wheat samples belonging to eight cultivars grown in a national network experimental trials over a three-year period (2011–2013). The effect of several factors (cultivar, year and cultivation area) affecting the occurrence of the two types of mycotoxins and their relationship with several agronomic and grain quality parameters were assayed by statistical analysis (GLZ). The results highlighted the different trend of incidence and contamination rate of the two types of mycotoxins in relation to the cropping year and to the growing examined areas. Year and its interaction with the cultivation area was the most important factor affecting the DON contamination, whereas genotype and its interaction with the year mainly influenced T2+HT2 toxins contamination rate. DON and T2+HT2 contamination levels were not significantly correlated with each other. The evidence that the two types of mycotoxins were differently related with several agronomic and grain quality parameters could be connected to the effects of the respective fungal disease on wheat plant.