Understanding the biological changes that precede a diagnosis of inflammatory bowel disease (IBD) could facilitate pre-emptive interventions, including risk factor modification, but this pre-clinical phase of disease remains poorly characterized. Using measurements from 17 hematological and biochemical parameters taken up to 10 years before diagnosis in over 20,000 IBD patients and population controls, we address this at massive scale. We observe widespread significant changes in multiple biochemical and hematological parameters that occur up to 8 years before diagnosis of Crohn’s disease (CD) and up to 3 years before diagnosis of ulcerative colitis. These changes far exceed previous expectations regarding the length of this pre-diagnostic phase, revealing an opportunity for earlier intervention, especially in CD. In summary, using a nationwide, case-control dataset—obtained from the Danish registers—we provide a comprehensive characterization of the hematological and biochemical changes that occur in the pre-clinical phase of IBD.