Prof Hilton began his scientific career in 1984 as a vacation student in Professor Ian Young's laboratory at the John Curtin School of Medical Research and in 1986 as a BSc(Hons) student at the Walter and Eliza Hall Institute of Medical Research (WEHI). Prof Hilton spent two years as a post-doctoral researcher at The Whitehead Institute, MIT in Cambridge working on the structure/function relationship of the erythropoietin receptor. Since returning to Australia in 1993 he has established an international reputation as a result of his discoveries in the area of cytokine signaling. Over the last three years Prof Hilton, with Prof Warren Alexander and Dr Benjamin Kile, established a new program using large-scale mouse genetics to dissect the molecular regulation of blood cell formation.

Prof Hilton was appointed to lead a Systems Biology initiative at WEHI at the beginning of 2006 and became Head of the Division of Molecular Medicine. In July 2009 Prof Hilton was appointed Director of the Walter and Eliza Hall Institute of Medical Research and Head of the Department of Medical Biology of the University of Melbourne. 

Prof Hilton is a Fellow of the Australian Academy of Science and in 2007 was awarded an inaugural NHMRC Australia Fellowship.