Coote returned to Australia in 2001 and joined the Research School of Chemistry, Australian National University as a postdoctoral fellow with Leo Radom. It was during this time that she began to build a reputation in computational chemistry, and she established an independent research group on the computer-aided chemical design at ANU in 2004.
Awarded an ARC Future Fellowship in 2010, Coote focused on a computer-guided experimental approach to understand and control the stereochemistry of free-radical polymerisation. Since then, Coote has received a number of grants from the Australian Research Council, including the Georgina Sweet Australian Laureate Fellowship in 2017. Today, her research interests span several broad areas of fundamental and applied chemistry: stereocontrol in free-radical polymerisation, polymer degradation and stabilisation, radical stability and, most recently, electric field effects on chemical reactivity.
Coote became the first female Professor of Chemistry at ANU in 2011.