Introduction In the past 2 decades, many tobacco control policies were enacted, and several new or modified products were introduced into the US marketplace. Continued tobacco surveillance is critical in this evolving landscape. We examined 20-year trends in tobacco use from sales and self-reported data. Methods We obtained data on taxable removals (sales) of cigarettes, cigars, roll-your-own (RYO) tobacco, and pipe tobacco from the US Department of the Treasury. We assessed self-reported past 30-day tobacco use from the National Survey on Drug Use and Health among people aged 18 years or older. Volume sales were standardized to cigarette packs and cigarette pack equivalents (CPEs) and trends measured by using joinpoint and logistic regression. Results From 2000 to 2019–2020, declines occurred in per capita sales of cigarettes (101.01 to 42.29 packs/capita), little cigars (0.54 to 0.03 CPEs/capita), and RYO tobacco (1.34 to 0.21 CPEs/capita). Volume sales also decreased for chewing tobacco and scotch/dry snuff (all P <.05). Conversely, volume sales increased for pipe tobacco, moist snuff, and snus for the respective assessed periods. Large cigar volume sales did not change significantly. We found consistent trends in self-reported use, except for RYO tobacco (decreased volume sales but increased self-reported use) and pipe smoking (increased volume sales, but trivial self-reported use <1% throughout the study period). Current use of any tobacco product decreased from 32.2% to 22.9% during the assessed period. Conclusion Harmonizing the tax and regulatory structure within and across the diversity of tobacco products may help reduce aggregate tobacco consumption in the US.