Multiple genome sequencing studies have identified the prevalence of clonal hematopoiesis of indeterminate potential (CHIP) in aged human populations. Still, little is known about the contribution and dynamics of hematopoietic clones during the lifespan of an individual. Here, we used a non-invasive in vivo color labeling system to observe changes in hematopoietic clonal complexity during the natural murine lifespan. During steady-state hematopoiesis, the clonal complexity of the peripheral blood (PB) was essentially stable until 20–24 months, at which point complexity decreased by 30% (p = 0.04). Meanwhile, the clonal complexity of different hematopoietic stem and progenitor cell bone marrow compartments (HSPC) in the bone marrow of aged mice decreased much more dramatically by 70–77% (p < 0.001). This discrepancy in complexity between the PB and the HSPC may be reflective of a substantial clonal expansion of the HSPC pool during aging, creating a mixture of HSPC in which the majority are compromised in their stem-like ability to contribute to the PB. This compromised population would likely mask the smallerbut more diverseHSPCs that actively contribute to the PB. Indeed, we detected an 18-fold increase in the number of immunophenotypic HSC in aged bone marrow (p = 0.001), yet aged HSC displayed reduced repopulating activity compared to young HSC. Further, our in vivo color labelling system allowed us to track the clonal dynamics of PB and bone marrow repopulation as young and aged bone marrow were serially transplanted. By tertiary and quaternary transplantation, most recipients displayed mono- or di-color PB and HSPC pools, reflective of clonal hematopoiesis. Whole exome sequencing is underway to identify molecular drivers of these predominant clones. Our study represents the first analysis of the evolving clonal complexity of hematopoiesis throughout the natural lifespan of the mouse.