Aquaponics is the integration of aquaculture and hydroponics. There is expanding interest in aquaponics as a form of aquaculture that can be used to produce food closer to urban centers. Commercial aquaponics uses methods and equipment from both the hydroponics and aquaculture industries. There have been few studies of commercial-scale aquaponics production, and the purpose of this research was to document the production methods, crop and fish yields, and profitability of commercial aquaponics in the United States (US) and internationally. An online survey was used for data collection, and 257 respondents met the inclusion criteria for the study. Eighty-one percent of respondents lived in the US, and the remaining respondents were from 22 other countries. The median year that respondents had begun practicing aquaponics was 2010. A total of 538 full-time workers, 242 part-time workers, and 1720 unpaid workers or volunteers were employed at surveyed organizations. The most commonly raised aquatic animals by percent were tilapia (69%), ornamental fish (43%), catfish (25%), other aquatic animals (18%), perch (16%), bluegill (15%), trout (10%), and bass (7%). Production statistics, gross sales revenue, investments, and sales outlets for operations are reported and compared to other fields of aquaculture and agriculture. A multivariable logistic regression model was used to study which factors were associated with profitability (as a binary outcome) in the past 12 months. Several factors were significantly associated with profitability: aquaponics as the respondents' primary source of income (p < 0.01; Odds Ratio: 5.79; 95% Confidence Interval: 3.8–9.0), location in US Department of Agriculture plant hardiness zones 7–13 (p < 0.01; OR: 4.17; 95% CI: 3.2–5.5), gross sales revenue ≥$5000 (p < 0.01; OR: 3.58; 95% CI: 2.2–5.8), greater aquaponics knowledge (p < 0.01; OR: 2.37; 95% CI: 2.0–2.9), and sales of non-food products (e.g., supplies, materials, consulting services, workshops, and agrotourism) (p = 0.028; OR: 2.13; 95% CI: 1.1–4.2). Our survey findings provide a better understanding of the business of aquaponics, which may enhance future commercial operations.