De Leeuw is interested in computational models of energy materials, biomaterials and minerals. She uses molecular dynamics and density functional theory. In 2000 she joined the University of Reading as a lecturer in Physical Chemistry. She was awarded an Engineering and Physical Sciences Research Council (EPSRC) Advanced Research Fellowship. She worked as an associate professor in computational materials science at Birkbeck, University of London, from 2004.
She was appointed a professor of computational materials science at University College London in 2007. De Leeuw designed computational models of olivine dust grains, a mineral that is common to the solar system, and studied how it interacted with water at high temperatures. She demonstrated that the grains could hold water at temperatures up to 630 °C. She studied the chemistry of hot vents on the sea floor, which De Leeuw proposed could produce the organic molecules essential for life. She has also investigated biomaterials, such as the carbonated hydroxyapatite present in bone and teeth. She investigated the nucleation of calcium carbonate. De Leeuw was awarded a Royal Society Wolfson Research Merit Award in 2010.
She was awarded a Royal Society industrial fellowship to study how radiation impacted materials for nuclear energy. In 2014 De Leeuw was awarded an Atomic Weapons Establishment (AWE) William Penney Fellowship. At University College London, De Leeuw directed the Centre for Doctoral Training (CDT) in molecular modelling & materials science. She is also a member of the EPSRC programme on energy materials. She uses computer-aided design to create new catalysts for the conversion of carbon dioxide to fuels.
De Leeuw joined Cardiff University in 2015. She was a member of the low-carbon economy research group, an EPSRC supported multi-institutional collaboration that looks to convert carbon dioxide to fuels and chemicals. She led the Cardiff University - Kwame Nkrumah University of Science and Technology - University of Namibia Chem4Energy programme, which developed novel solar materials and benign catalysts. She holds a professorship in theoretical geochemistry at Utrecht University and University of Paris-Est.
At Cardiff University, de Leeuw worked on the university's European strategy and collaborations. These included Horizon 2020, the Erasmus Programme and the Bologna Process.
On 31 May 2019, it was announced that de Leeuw would take up the newly created post of executive dean in the newly formed Faculty of Engineering and Physical Sciences at the University of Leeds on 1 January 2020.