Clinics and community-based organizations (CBOs) are priority settings for implementing the evidence-based National Diabetes Prevention Program (DPP). Both program settings present theoretical advantages and disadvantages for engaging and helping populations most at risk for diabetes achieve lifestyle change goals. To date, few studies have compared implementation across them. The present study describes participant characteristics and lifestyle change outcomes across a sample of clinic- and community-based National DPPs which delivered services in Los Angeles during 2015 to 2018 (two clinics, two CBOs, combined n = 265 participants). Analyses examined participant gender, age, race/ethnicity, baseline body mass index, and program attributes such as screening method and language of instruction. Negative binomial regression models tested for differences in program attendance, mean weekly physical activity, and percent change in body weight by setting. Overall, participants were largely Hispanic/Latinx (81.51%) and female (90.19%). Programs operated by CBOs engaged other race/ethnic groups including Black participants more frequently than those operated by clinics (20.56% vs. 0%); the latter engaged more men (15.29% vs. 7.22%). Few participants in any setting met the National DPP's weight loss goal (clinic: 15.29%, CBO: 20.00%). Participating in a community-based program was initially associated with higher attendance and mean weekly physical activity, but associations were not significant after adjusting for covariates. Study results have practice implications for National DPP implementation and can help inform future efforts to scale and spread the program in Los Angeles and nationally.