The purpose of this study was to determine the prevalence of chronic conditions and functional difficulties of American Indian/Alaska Native (AIAN) children with special health care needs (CSHCN). We conducted bivariate and multivariable analysis of cross-sectional data on 40,202 children from the 2009-2010 National Survey of Children with Special Health Care Needs aged birth through 17 years, including 1,051 AIAN CSHCN. The prevalence of AIAN CSHCN was 15.7 %, not significantly different from the prevalence of US white CSHCN (16.3 %). As qualifiers for special needs status among AIAN children the use of or need for prescription medication was the most frequent (70 %), compared to the lower rates of need for elevated service use (44 %) and emotional, mental, or behavioral treatment/counseling (36 %). Asthma (45 %), conduct disorder (18 %), developmental delay (27 %), and migraine headaches (16 %) were significantly more common chronic conditions among AIAN CSHCN compared to white CSHCN, as were functional difficulties with respiration (52 %), communication (42 %), anxiety/depression (57 %), and behavior (54 %). AIAN CSHCN were also more likely to have 3 or more chronic conditions (39 vs. 28 %, respectively) and 3 or more functional difficulties (70 vs. 55 %, respectively) than white CSHCN. Results indicated a greater impact on the daily activities of AIAN CSHCN compared to white CSHCN (74 vs. 63 %). Significantly greater disease burden among AIAN CSHCN suggests that care must be taken to ensure an appropriate level of coordinated care in a medical home to ameliorate the severity and complexity of their conditions.