ISO 50001 and other management systems (e.g., ISO 9001 and ISO 14001) allow for implementation and certification at the enterprise level. The "Central Office" concept, which allows a small group of employees to manage and facilitate the organization’s energy management system (EnMS) at the enterprise level, was introduced within the ISO 50003 standard to provide guidance to ISO 50001 certification bodies. Four industrial companies have partnered with the United States Department of Energy to pilot the enterprise-wide ISO 50001/SEP concept under the Better Buildings Superior Energy Performance (SEP) Enterprise-wide Accelerator. Each organization developed a Central Office to host their EnMS while implementing ISO 50001/SEP at multiple physically separated sites. The four corporate partners tailored their Central Office implementation model to meet their own specific circumstances and needs. This paper reviews the commonalities, differences, and benefits of each of these enterprise-wide implementation models, including organizational structures, Central Office staff responsibilities, and key strategies. The cost savings and benefits of using the enterprise-wide approach were assessed, including the cost per site compared with that of a conventional, single-site ISO 50001/SEP implementation approach. This paper also discusses the drivers for the cost reductions realized through these enterprise-wide approaches. The four partner companies worked with 30 total sites. On average, these 30 sites improved energy performance by 5% annually over their SEP achievement periods, saved more than $600,000 annually in energy costs and reduced implementation cost for ISO 50001 and SEP by $19,000 and 0.8 Full Time Equivalent × years (FTE-yr) of staff time per site. The results can inform other organizations seeking to implement enterprise-wide ISO 50001/SEP, as well as energy efficiency organizations seeking to promote wider adoption of ISO 50001 implementation.