The department was established in 1968 under the name og the Department of Molecular Biology and was housed in the so-called "Biokæden" at Aarhus University Campus (buildings 1130-1135). The department has changed its name several times (Institute for Molecular Biology and Plant Physiology, Department of of Molecular and Structural Biology, Department of Molecular Biology) in connection with mergers with other sections and departments.

On 1 July 2011, the Department of Molecular Biology and Genetics (MBG) was created by merging the Department of Molecular Biology (excluding the research groups within Lipid Biochemistry and Engineering) and the research groups within Molecular Genetics and Biotechnology, Molecular Genetics and System Biology, Quantitative Genetics and Biostatistics from the Department of Genetics and Biotechnology localised at Foulum (by Viborg) and  Flakkebjerg (by Slagelse).

The department's activities are currently spread over five different locations (Research Centre Foulum, Research Centre Flakkebjerg and in three different buildings in Aarhus - the "Biokæden" (Campus), the Science Park Gustav Wieds Vej and the iNANO house), but the plan is to move to a building close to Campus that will accommodate all staff and students of the department.