Introduction: In the United States, dentists frequently prescribe hydrocodone. In October 2014, the US Drug Enforcement Administration rescheduled hydrocodone from controlled substance schedule III to II, introducing more restricted prescribing and dispensing regulations, which may have changed dental prescribing of opioids. Objective: The study aim was to evaluate the impact of the hydrocodone rescheduling on dental prescribing of opioids in the United States. Methods: This was a cross-sectional study of opioids prescribed by dentists between October 2012 and October 2016, using the IQVIA Longitudinal Prescription Dataset. Monthly dentist-based opioid prescribing rate (opioid prescription [Rx]/1,000 dentists) and monthly average opioid dosages per prescription (mean morphine milligram equivalent per day [MME/d]) were measured in the 24 mo before and after hydrocodone rescheduling in October 2014 (index or interruption). An interrupted time-series analysis was conducted using segmented ordinary least square regression models, with Newey–West standard errors to handle autocorrelation. Results: Dentists prescribed 50,412,942 opioid prescriptions across the 49 mo. Hydrocodone was the most commonly prescribed opioid pre- and postindex (74.9% and 63.8%, respectively), followed by codeine (13.8% and 21.6%), oxycodone (8.1% and 9.5%), and tramadol (2.9% and 4.8%). At index, hydrocodone prescribing immediately decreased by −834.8 Rx/1,000 dentists (95% confidence interval [CI], −1,040.2 to −629.4), with increased prescribing of codeine (421.9; 95% CI, 369.7–474.0), oxycodone (85.3; 95% CI, 45.4–125.2), and tramadol (111.8; 95% CI, 101.4–122.3). The mean MME increased at index for all opioids except for hydrocodone, and dosages subsequently decreased during the postindex period. Conclusion: Following the rescheduling, dentist prescribing of hydrocodone declined while prescribing of nonhydrocodone opioids increased. Understanding the impact of this regulation informs strategies to ensure appropriate prescribing of opioids for dental pain. Knowledge Transfer Statement: The study findings can be used by policy makers to make informed decisions in developing future risk mitigation strategies aimed to regulate opioid prescribing behaviors. Furthermore, dentist-specific resources and guidelines are needed subsequent to these policies in order to meet the dental population needs.