The tremendous changes in the 21st century is the emerging nature of a new set of economic and social indicators which eventually capture the changes in structural transformation, technological advance, and competition in the job market. Such evolutions have driven changes in skills required to compete effectively in today’s global economy. This paper aims to discuss the development and validation process of the Malaysian 21st century skills instrument (M-21CSI) to be used within the teaching and learning of science processes. The Malaysian 21st Century Skills Instrument (M-21CSI) consists of five distinctive elements which are: i) Digital Age Literacy; ii) Inventive Thinking; iii) Effective Communication; iv) High Productivity; and iv) Spiritual Value. Through extensive review of the literature and group discussion, constructs that represent the Malaysian 21st Century Skills were identified and further refined by Two Round Delphi Studies. Subsequent to that, items representing each construct were then drawn up. In order to justify the validity of this instrument, four experts were invited to review the instrument. This then was followed by factor a analysis. The reliability of each construct was justified in terms of its internal consistency by means of Cronbach Alpha. Findings of this study confirmed the validity and reliability of the M-21CSI and thus show that it is a useful instrument to evaluate the mastery of Malaysian students towards 21st century skills.