ImportanceHealth systems in the US are increasingly screening for social determinants of health (SDOH). However, guidance incorporating stakeholder feedback is limited.ObjectiveTo examine patient and care team experiences in early implementation of SDOH screening in primary care.Design, Setting, and ParticipantsThis qualitative study included cross-sectional analysis of SDOH screenings during primary care visits from February 22 to May 10, 2022, primary care team member interviews from July 6, 2022, to March 8, 2023, and patient stakeholder engagement on June 30, 2022. The setting was a large southeastern US health care system. Eligible patients were aged 18 years or older with completed visits in primary care.ExposureScreening for SDOH in primary care.Main outcomes and MeasuresMultivariable logistic regression evaluated patient (eg, age, race and ethnicity) and care team characteristics (eg, practice type), and screening completeness. Interviews contextualized the quantitative analysis.ResultsThere were 78 928 visits in practices conducting any SDOH screening. The population with visits had a mean (SD) age of 57.6 (18.1) years; 48 086 (60.9%) were female, 12 569 (15.9%) Black, 60 578 (76.8%) White, and 3088 (3.9%) Hispanic. A total of 54 611 visits (69.2%) were with a doctor of medicine and 13 035 (16.5%) with a nurse practitioner. Most had no SDOH questions answered (75 298 [95.4%]) followed by all questions (2976 [3.77%]). Logistic regression analysis found that clinician type, patient race, and primary payer were associated with screening likelihood: for clinician type, nurse practitioner (odds ratio [OR], 0.13; 95% CI, 0.03-0.62; P = .01) and physician assistant (OR, 3.11; 95% CI, 1.19-8.10; P = .02); for patient race, Asian (OR, 1.69; 95% CI, 1.25-2.28; P = .001); Black (OR, 1.49; 95% CI, 1.10-2.01; P = .009); or 2 or more races (OR, 1.48; 95% CI, 1.12-1.94; P = .006); and for primary payer, Medicaid (OR, 0.62; 95% CI, 0.48-0.80; P < .001); managed care (OR, 1.17; 95% CI, 1.07-1.29; P = .001); uninsured or with Access Health (OR, 0.26; 95% CI, 0.10-0.67; P = .005), and Tricare (OR, 0.71; 95% CI, 0.55-0.92; P = .01). Interview themes included barriers (patient hesitancy, time and resources for screening and referrals, and number of questions/content overlap) and facilitators (communication, practice champions, and support for patient needs).Conclusions and RelevanceThis qualitative study presents potential guidance regarding factors that could improve SDOH screening within busy clinical workflows.