Leukemia is a malignant progressive disease and has four major subtypes. Different racial groups differ significantly in multiple aspects. Our goal is to systematically and comprehensively quantify racial differences in leukemia. The SEER database is analyzed, and comprehensive descriptive analysis is provided for the four major subtypes, namely ALL (acute lymphoblastic leukemia), CLL (chronic lymphoblastic leukemia), AML (acute myeloid leukemia), and CML (chronic myeloid leukemia), and for two age groups (≤14 and >14) separately. The racial groups studied include NHW (non-Hispanic White), HW (Hispanic White), BL (Black), and API (Asian and Pacific Islander). Univariate and multivariate analyses are conducted to quantify racial differences in patients' characteristics, incidence, and survival. For patients' characteristics, significant racial differences are observed in gender, age at diagnosis, diagnosis era, using radiation for treatment, registry, cancer history, and histology type. For incidence, significant racial differences are observed, and the patterns vary across subtypes, gender, and age groups. For most of the subtypes and gender and age groups, Blacks have the worst five-year survival, and significant racial differences exist. This study provides a comprehensive epidemiologic description of racial differences for the four major leukemia subtypes in the U.S.