The success of early-career faculty at R1 research-intensive institutions depends on institutions’ ability to establish an independent, grant-funded research program in a highly competitive funding environment in which only 2,174 of 11,463 National Institutes of Health (NIH) applications (19%) submitted by early-stage investigators were funded in 2023. This report summarizes outcomes of early-career faculty enrolled in the University of California San Diego Health Sciences Grant Writing Course (GWC), which provided a structured, step-by-step, multicomponent experience focused on preparing a competitive grant proposal. The program evaluation includes effects on grant submission and funding rates and grant-writing self-efficacy after 2 years of follow-up. Eighty-five early-career faculty members were enrolled in the GWC from 2017 to 2021, including 48 (56%) MD and MD-PhD physicians, 37 (44%) PhD faculty, 45 (53%) women, and 15 (18%) self-identifying as being from underrepresented racial or ethnic backgrounds. Data from 82 participants (98%) at 12 or 24 months were used for grant outcomes, and 75 participants (88%) with 12- and 24-month data were used in the self-efficacy analysis. Seventy-one participants (87%) submitted their course proposal, and 79 (96%) submitted at least one grant application by the 2-year follow-up. Thirty-three GWC proposals (40%) were funded, and 65 participants (79%) received at least one grant as principal investigator or multiple principal investigator since taking the course. Success rates were equal for men (26 [79%]) and women (34 [79%]) and highest (12 [86%]) for underrepresented faculty. Of the funded proposals, 49 (30%) were NIH R01, R01-equivalent, or R21 awards. Underrepresented participants had the highest (19 [48%]) success rate. Participants’ confidence in the 19 grant-writing skills inventory increased overall. The GWC is a highly effective and innovative program for improving grant-writing success of early-career, women, and underrepresented faculty in academic medicine.