Universal health coverage requires an adequate health workforce, including community health workers (CHWs) to reach rural communities. To improve healthcare access in rural areas, in 2010 the Government of Zambia implemented a national CHW strategy that introduced a new cadre of healthcare workers called community health assistants (CHAs). After 1 year of training the pilot class of 307 CHAs deployed in September 2012. This paper presents findings from a process evaluation of the barriers and facilitators of implementation of the CHA pilot, along with how evidence was used to guide ongoing implementation and scale-up decisions. Qualitative inquiry was used to assess implementation during the first 6 months of the program rollout, with 43 in-depth individual and 32 small group interviews across five respondent types: CHAs, supervisors, volunteer CHWs, community members, and district leadership. Potential ‘implementation moderators’ were explored using deductive coding and thematic analysis of participant perspectives on community acceptance of CHAs, supervision support mechanisms, and coordination with volunteer CHWs, and health system integration of a new cadre. Community acceptance of CHAs was generally high, but coordination between CHAs and existing volunteer CHWs presented some challenges. The supervision support system was found to be inconsistent, limiting assurance of consistent quality care delivered by CHAs. Underlying health system weaknesses regarding drug supply and salary payments furthermore hindered incorporation of a new cadre within the national health system. Recommendations for implementation and future scale based on the process evaluation findings are discussed.