The construction industry in Ethiopia plays a significant role for the development of the country. However, the construction sector faces multiple challenges; including schedule delay, cost overrun and dispute among major parties. Prior studies also reveal that, among others, design change is one of the primary factors contributing to these problems and drawbacks. In this context, the primary objective of this research is to identify and analyze the major causes that lead to design change in the implementation phase of construction projects. In addition, the study aims to examine the impacts of design change, along with quantifying the overall effects of design change in terms of cost overrun and time variance during the design and construction stages of both road and building projects across the Amhara National Regional State.To achieve these goals 48 critical causes and 7 impacts of design changes were identified through a systematic literature review,23 key causes and 7 impacts were then refined according to the opinions of relevant experts involved in Amhara Region Road and building projects. Then, various data collection method was employed, including a structured questionnaire survey, desk study and interviews. More so, 31 projects were identified as part of the case studies conducted to evaluate the impacts of design change in the cost and time overrun of infrastructure projects. The study analyzed the collected data by Interpretive Structural Modeling (ISM) and to classify the causes using the “Matrice d’Impacts Croisés Multiplication Appliquée à un Classement” MICMAC technique. The result showed that Inadequate project objectives, Unrealistic clients demand , Obstinate nature of client, Inconsistency of drawing with Bill of Quantity, Design error, Inconsistent site condition and information, Ineffective utilization of automation , Unforeseen ground condition and Difference between design standard and reality, which have strong driving power and significantly influence other causes, should be given more emphasis.The findings of the study are expected to help construction organizations, practitioners, and policy makers to trap the key factors affecting design changes in infrastructure projects across the Ethiopian construction industry. Keywords: design change; interpretive structural modeling; cause and impact; road and building projects