Khlobystov started his post-doctoral career at the Department of Materials at the University of Oxford from 2002 until 2004 under Andrew Briggs, where he began exploring carbon nanotube as nanoscale containers for molecules. He applied transmission electron microscopy (TEM) for imaging structures of individual molecules and studying their dynamic behaviour in direct space and real time, which shed light on intermolecular interactions, and the translation and rotational motion of molecules at nanoscale. In his time at Oxford he was part of the team awarded a Guinness World Record for performing a chemical reaction inside carbon nanotubes.
In 2004, Khlobystov moved to the University of Nottingham as a Leverhulme Trust research fellow. At Nottingham, he built the Nottingham Nanocarbon Group, which has demonstrated that nanoscale confinement can lead to new products inaccessible by other synthetic methods. In 2005, his research group was awarded a European Young Investigator award and a Royal Society University Research Fellowship. Around this time, he was featured in Times Higher Educations series of emerging researchers in the physical sciences. In 2008, the Nanocarbon Group presented at the Royal Societys Summer Science Exhibition, with a display entitled "Wonder in carbon land: how do you hold a molecule?", showcasing the potential of utilising nanocages and nanotubes to control chemical reactions. Khlobystov's team has discovered mechanisms of interactions between carbon nanostructures and molecules or nanoparticles which enabled the design of nanoreactor systems with tuneable size and functionality. This research was supported by numerous grants including a European Research Council Starting Grant in 2011.
In 2016, to commemorate the opening of the nano- and micro-Research Centre (nmRC) at the University of Nottingham, Khlobystov led a team that utilised a Focused Ion Beam Scanning Electron Microscope (FIB-SEM) to etch a birthday message onto a corgi hair to commemorate Queen Elizabeth II's 90th birthday. In 2020, Khlobystov led a team that captured a video of the chemical bond between two metal atoms breaking and forming for the first time. This followed previous work which embraced the observer effect, utilising the electron beam present in an electron microscopy to provide the source of energy to drive chemical reactions and enable them to be directly observed, and was given the moniker ChemTEM.
Since 2021, Khlobystov has been PI for the MASI programme grant, which is investigating solvent-free routes to preparing and understanding single metal atoms and metal nanoclusters on surfaces for use as catalysts for electrochemical hydrogen production, ammonia synthesis and carbon dioxide reduction.