Giardiasis is the most commonly reported intestinal parasitic infection in the United States. Outbreak investigations have implicated poorly maintained private wells, and hypothesized a role for wastewater systems in giardiasis transmission. Surveillance data consistently show geographic variability in reported giardiasis incidence. We explored county-level associations between giardiasis cases, household water and sanitation (1990 census), and US Census division. Using 368,847 reported giardiasis cases (1993–2010), we mapped county-level giardiasis incidence rates, private well reliance, and septic system reliance, and assessed spatiotemporal clustering of giardiasis. We used negative binomial regression to evaluate county-level associations between giardiasis rates, region, and well and septic reliance, adjusted for demographics. Adjusted giardiasis incidence rate ratios (aIRRs) were highest (aIRR 1.3; 95% confidence interval 1.2–1.5) in counties with higher private well reliance. There was no significant association between giardiasis and septic system reliance in adjusted models. Consistent with visual geographic distributions, the aIRR of giardiasis was highest in New England (aIRR 3.3; 95% CI 2.9–3.9; reference West South Central region). Our results suggest that, in the USA, private wells are relevant to giardiasis transmission; giardiasis risk factors might vary regionally; and up-to-date, location-specific national data on water sources and sanitation methods are needed.