Objectives. To estimate Tobacco-21 policies' relationships to 18- to 20 year-old youth cigarette, cigar, and electronic nicotine delivery system (ENDS) use, and to test for effect modification by policy attributes. Methods. In fall 2022, we used Tobacco 21 Population Coverage Database data to calculate the percentage of state residents covered by state or local Tobacco 21 (T21) laws monthly through June 2020. Matching T21 coverage to Population Assessment of Tobacco and Health and Behavioral Risk Factor Surveillance System data, we used 2-way fixed effect analyses to assess the relationship between T21 laws and 18- to 20-year-old youth cigarette, cigar, and ENDS use, and tested for differences by policy attributes: possession, use, or purchase (PUP) penalties, retailer noncompliance penalties, and compliance check requirements. Results. Increased T21 exposure yielded significant reductions in cigarette and cigar use, as well as in ENDS use, when accounting for policy attributes. These effects were dampened in T21 laws with PUP penalties relative to those without. Conclusions. Tobacco-21 laws yield reductions in 18- to 20-year-old youth cigarette, cigar, and ENDS use, with dampened effects when policies include PUP penalties. Public Health Implications. State policymakers should consider implementing T21 laws without PUP penalties to reduce underage nicotine and tobacco use. (Am J Public Health. 2024;114(1):90-97. https://doi.org/10.2105/AJPH.2023.307447).