Epigenetic regulators, ASXL1, DNMT3A, and TET2 are frequently mutated in clonal hematopoiesis (CH). Dnmt3a- or Tet2-deficient mice increase self-renewal of hematopoietic stem cells (HSCs), suggesting that mutations in DNMT3A and TET2 provoke clonal expansion of hematopoietic cells, leading to subsequent CH in humans. On the contrary, ASXL1-mutated mice show reduced numbers and functions of HSCs. Thus, how ASXL1 mutations drive CH are not understood. Here, we investigated the effects of ASXL1 mutations on physiological aging of HSCs using knockin (KI) mice expressing a C-terminally truncated form of ASXL1 (ASXL1-MT). We found that HSCs expressing ASXL1-MT exhibited a competitive disadvantage after transplantation. On the other hand, in a genetic mosaic mouse, they displayed a growth advantage to occupy the HSC compartment over time, recapitulating CH in humans. As a mechanism by which ASXL1-MT causes CH, we show that ASXL1-MT binds and stabilizes phosphorylated Akt to activate Akt/mTOR pathway in coordination with Bap1. Activated Akt/mTOR induces dysregulated cell cycle progression and proliferation of HSCs. Meanwhile, it also compromises HSC functions along with activated mitochondrial metabolism, ROS overproduction, and increased DNA damage. Treatment with an mTOR inhibitor rapamycin suppressed aberrant proliferation of HSCs and ameliorated dysregulated hematopoiesis in aged ASXL1-MT KI mice. Taken together, ASXL1-MT impairs function of HSCs, whereas it confers a clonal advantage on HSCs during aging specifically in native hematopoiesis. ASXL1 mutation-mediated expansion of HSCs associated with increased DNA damage can induce development of CH, resulting in malignant transformation with secondary mutations. Akt/mTOR signaling could be a therapeutic target to individuals with CH harboring ASXL1 mutations.