During pulling experiments or structural tasks in living and artificial environments, double-stranded DNA could be subjected to external tensile loadings that are not parallel with the helix axis of DNA. The aim of this work is to simulate the shear stretching of duplex DNA oligonucleotides via atomic force microscopy (AFM) at the atomistic scale. We focus on the response of the molecule to the process of angled pulling and conduct a series of modified steered molecular dynamics simulations with a generalized Born/surface area approach. The force–extension curves obtained from the implicit and explicit solvent simulations show very good agreement, providing an additional support for the use of the proposed implicit solvent model for DNA pulling simulations. The results reveal that pulling dsDNA at different angles may produce a variety of unexpected mechanical responses and unusual conformations. The values of the ultimate force used and ensuing displacements may depend significantly on the initial angle of stretching. However, the error introduced for the prediction of the DNA ultimate force is not significant if the DNA stretching initiates at angles smaller than 30°.