A way of presenting information in visual representations of technical systems influences the progress and the outcome of the engineering design process. Consequently, an improvement of the means by which information is utilized (generated and interacted with) during the process is one suggested approach of advancing engineering design. Although engineers’ interaction with information has been mostly visual, virtual, and cognitive, little is known about cognition (mental information processing) underlying generation of and interaction with visual representation of technical systems during engineering design. With the aim of narrowing this research gap, the presented study explored the effects of visual representations of technical systems to engineers’ brain activity while generating computer-aided design (CAD) models based on them. More precisely, brain activity of 20 engineers was monitored and analysed using electroencephalography (EEG) during the visuospatially-intensive design tasks of CAD modelling in two conditions; when technical systems were presented with orthographic and isometric projections in technical drawings. Significant differences and effect sizes were found among the total signal and individual band (theta, alpha, and beta) task related power (TRP) both when interpreting the projections in technical drawings and generating 3D CAD models from them. The results suggest that significant differences exist in brain activity when considering the individual electrodes, all the 14 electrodes cumulatively (the TRP across the cortex), the cortical hemispheres, and the cortical areas. In particular, the TRP was persistently higher when interpreting the technical drawing with orthographic projection and generating a CAD model from it. In addition, theta TRP in frontal brain area seems to be particularly important in distinguishing neurocognitive responses to the orthographic and isometric projections. As such, the conducted exploratory study grounds a basis for exploring engineers’ brain activity while solving visuospatially-intensive design tasks, whose segments are relatable to the aspects of visuospatial thinking. Future work will explore brain activity in other design activities that are highly visuospatial in their nature, with a larger sample size and an EEG device of a higher spatial resolution.