Hookah tobacco smoking is associated with substantial toxicant exposures and is increasing among college students in the United States. Greek (fraternity/sorority) students, especially those living in Greek housing, have high rates of risky alcohol use. The extent to which this is true for other substances, including hookah tobacco smoking, is not well known. The objective of this study is to examine associations between Greek involvement and living arrangement (non-member, non-resident member, resident member) and rates of hookah tobacco smoking, in relation to other substances, among US college students. We used national data from 82,251 student responses from the 2008 to 2009 administration of the National College Health Assessment. Generalized estimating equations were utilized to determine adjusted odds ratios for substance use outcomes based on involvement and living arrangements, while adjusting for covariates and clustering of students within institutions. Among resident members, ever use was highest for marijuana (52.4 %), hookah (48.5 %) and cigarettes (46.6 %). In multivariable models, adjusted odds were lowest for non-Greeks and highest for Greek resident members. Compared to non-Greeks, Greek resident members had nearly double the odds for current use of hookah, cigars, and marijuana, as well as two and a half times the odds for current use of smokeless tobacco and three times the odds for alcohol bingeing. Similar to other substances, hookah tobacco smoking is highest among Greek resident members, compared with both Greeks living outside Greek housing and non-Greeks. It is valuable for substance use surveillance and intervention to focus on Greek resident members.