We aimed to evaluate the incidence of chronic renal injury in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitors (TKIs) and to identify the associated factors. Data for CML-CP patients with normal estimated glomerular filtration rate (eGFR) at baseline and receiving TKI therapy ≥ 3 months were retrospectively reviewed. The CRAE (chronic renal adverse event, defined as a 30% eGFR reduction from baseline or eGFR < 60 ml/min/1.73 m2 ≥ 90 days whichever occurred first)-free survival rates at 3 years in the imatinib cohort (n = 360) were significantly lower than those in the nilotinib cohort (n = 100) (55% versus 77%, P = 0.001) as a first-line TKI therapy. In multivariate analyses, imatinib, male sex, increasing age, and previous non-TKI treatment were associated with poor CRAE-free survival. In newly diagnosed patients who received imatinib treatment (n = 40), 24-h urine protein levels significantly increased after 6 months, and urinary β2-microglobulin values significantly increased compared to those in the nilotinib cohort (n =15) at 36 months (P = 0.042) and 42 months (P = 0.039). There was no significant difference in CRAE-free survival rates at 3 years between the nilotinib (n = 65) and dasatinib (n = 74) cohorts (67% versus 83%, P = 0.832) as second- or third-line TKI therapies. In multivariate analyses, previous non-TKI treatment was associated with poor CRAE-free survival. We concluded that imatinib was significantly correlated to chronic renal injury, possibly associated with glomerulus and renal tubular injury, compared with nilotinib as a first-line TKI therapy in CML-CP patients. However, nilotinib and dasatinib had similar mild adverse impacts on renal function as second- or third-line therapies.