A biochemist by training, George was initially involved in the field of Computational Biology following a MSc degree by research on correlated mutations analysis on G-Protein coupled receptors which involved modelling class A G-Protein Coupled Receptors (GPCRs) and drug design. He then proceeded to obtain a PhD in the areas of Chemoinformatics/Bioinformatics at Imperial College of London.

After the completion of his PhD, he was awarded a MRC Career Development Fellowship at MRC Harwell, Oxford. In 2005, he joined the Department of Genetics at Cambridge University and was part of various international consortia aimed at facilitating the translation of basic research findings to applications that aimed at the identification of the genetic underpinnings of disease mechanisms. In 2012, he became the head of the Bioinformatics and Computational Biology Group at Aberystwyth University, an interdisciplinary group of bioinformatics researchers, working at the interface between computing, biology and medical applications and crossing the Department of Computer Science and the Institute of Biological, Environmental and Rural Sciences (IBERS). George maintains an Aberystwyth University honorary Professorship in Bioinformatics.

In September 2015, George joined the University of Birmingham as the Chair of Clinical Bioinformatics. Professor Gkoutos splits his time between the Centre of Computational Biology, the College of Medical and Dental Sciences, the Institute of Translational Medicine and the Queen Elizabeth Hospital.