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Background: Substance use disorders (SUDs) among people with HIV are both prevalent and problematic. The Substance Abuse Treatment to HIV care project was funded to test the Implementation and Sustainment Facilitation (ISF) strategy as an adjunct to the Addiction Technology Transfer Center (ATTC) strategy for integrating a motivational interviewing-based brief intervention (MIBI) for SUDs within HIV community-based organizations. Methods: Using a cluster-randomized, type 2 hybrid trial design, 39 HIV organizations were randomized to either (1) ATTC ( n = 19) or (2) ATTC + ISF ( n = 20). Each HIV organization identified two staff members to be prepared to implement the MIBI ( N = 78). Subsequently, during the implementation phase, HIV organizations in each condition randomized client participants ( N = 824) to one of the two intervention conditions: usual care (UC; n = 415) or UC + MIBI ( n = 409). Both staff-level outcomes and client-level outcomes were examined. Results: The ISF strategy had a significant impact on the implementation effectiveness (i.e., the consistency and the quality of implementation; β = .65, p = .01) but not on time-to-proficiency (β = −.02) or level-of-sustainment (β = .09). In addition, the ISF strategy was found to have a significant impact on the intervention effectiveness (the effectiveness of the MIBI), at least in terms of significantly decreasing the odds (odds ratio = 0.11, p = .02) of clients using their primary substance daily during follow-up. Conclusion: The ISF strategy was found to be an effective adjunct to the ATTC strategy in terms of implementation effectiveness and intervention effectiveness. It is recommended that future efforts to integrate the project’s MIBI for SUD within HIV organizations use the ATTC + ISF strategy. However, given the ISF strategy did not have a significant impact on level-of-sustainment, implementation research testing the extent to which the ATTC + ISF strategy can be significantly enhanced through effective sustainment strategies is warranted. Plain language abstract Substance use among people living with HIV is associated with increased mental health problems, worse medication adherence, and worse HIV viral suppression. Increasing substance use-related services in HIV community-based organizations is an important public health need. The Substance Abuse Treatment to HIV care project tested two strategies for helping HIV organizations implement a brief intervention (BI) designed to motivate clients to decrease their substance use. The project also tested if receiving a BI improved clients’ outcome. Two staff from each of the 39 participating organizations were taught how to deliver the BI using the Addiction Technology Transfer Center (ATTC) training strategy (online and in-person training, monthly feedback, and coaching). Half of the organizations also received the Implementation and Sustainment Facilitation (ISF) strategy, which included monthly meetings with an ISF coach for the two BI staff and one or more leadership staff from the organization. Organizations that received both the ATTC and ISF strategies delivered more BIs and higher quality BIs than organizations that only received the ATTC strategy. In addition, clients receiving BIs at organizations that received both strategies were more likely to decrease their substance use. However, receiving both strategies did not improve how quickly staff learned to deliver the BI or improve the number of BIs delivered during the project’s 6-month sustainment phase. Future research focused on implementing BIs within HIV organizations should consider using the ATTC and ISF strategies while also seeking to enhance the strategies to improve sustainment.