Recently, the automotive industry has shown a growing interest in replacing conventional automotive mirrors with camera monitor systems (CMS) as CMS may provide multiple advantages, including the enhancement of driving safety through the human factors design of display layout. Despite past research, however, pertinent CMS display layout design guidelines have not been firmly established, due to insufficient empirical knowledge. To alleviate the current research gaps and inform the optimal design, this study comparatively evaluated twelve CMS display layout designs employing driving performance and eye glance behavior measures: six separate display layouts (three with the side-view displays near the A-pillars, and, three, on each side of the steering wheel), and, six integrated display layouts (three “segmented” and three “stitched” view layouts). Each design was evaluated in a safety-critical and a less safety-critical lane change scenario. The study demonstrated that the display layout design effects could vary across different driving task scenarios.