A closed-vessel microwave digestion method was developed for the simultaneous determination of macro, micro, and toxic elements (Mg, K, Ca, Al, Mn, Fe, Cu, Zn, Se, Rb, V, Cd, and As) in wheat by inductively coupled plasma mass spectrometry (ICP-MS). A two-level factorial design with four variables was employed to determine the optimal conditions for the significant parameters. The optimal conditions for microwave digestion of ground wheat samples were found to be 0.5 g of the sample, 9 mL of 8 mol/L HNO3, and 3 mL of 33% H2O2 at 210°C. The analytical method was validated, and the accuracy of the method was then evaluated through analysis of wheat flour-certified standard reference materials (NIST SRM 1567b). The validated procedure was subsequently applied to the analysis of 12 wheat samples sourced from local farms in the Al-Qassim region and a further six samples purchased from the Al-Qassim markets, covering six imported brands common in Saudi Arabia. The results of the study showed that the level of minerals in wheat grown in desert areas is higher than in other areas. The concentrations of macroelements and microelements in the Al-Qassim samples exceeded those of the imported samples by 12.41% and those of the samples from other countries by 33.90%. The results were also evaluated using multivariate analysis techniques: principal component analysis (PCA) and hierarchical cluster analysis (HCA).