MOSTI was first established in 1973 as the Ministry of Technology, Research and Local Government. In 1976, the ministry was re-established as the Ministry of Science, Technology and Environment (MOSTE) to include new functions and responsibilities related to environment. 

In 2004, the Government decided to restructure MOSTE as the Ministry of Science, Technology and Innovation (MOSTI) in order for it to spearhead the development of the National ICT, Multimedia and Innovation. Soon after in 2007, the ministry’s functions of Science and Technology were defined according to the clusters of Biotechnology, ICT, Industrial, Sea to Space and Core Cluster of Science & Technology.

In keeping up with developments, MOSTI was restructured in 2016 to give more focus on promoting R&D and commercialisation programmes. In 2018, the entire components of MOSTI, the Green Technology and Energy components from the Ministry of Energy, Green Technology and Water (KeTTHA) and related components of Climate Change and Environment under the Ministry of Natural Resources and Environment (NRE) were restructured and placed under the ministry named Ministry of Energy, Science, Technology, Environment & Climate Change (MESTECC).

In March 2020, MESTECC was restructured as MOSTI. MOSTI is the Lead Ministry for Malaysia’s participation at Expo 2020 Dubai. Malaysia Pavilion’s theme is “Energising Sustainability” with four sub-themes of Energising Today, Energising Tomorrow, Energising Business and Energising Harmony.

The Minister of Science,Technology and Innovation Malaysia is The Hon. Khairy Jamaluddin. MOSTI Secretary-General, Datuk Ir. Dr. Siti Hamisah Tapsir, also holds the position of Commissioner General of Malaysia for Malaysia Pavilion at the Expo 2020 Dubai while Deputy Secretary-General (Technology Development, Commercialisation & STI Services) Dr. Mohd Nor Azman Hassan is the Deputy Commissioner General of the Malaysia Pavilion. The Main Secretariat that oversees the planning of Malaysia Pavilion programmes is chaired by MOSTI Technology Transfer and Commercialisation of R&D Division Under Secretary Dr. Nor Azlina Ariffin.