Recent studies developing benchmarks using generic data and assumptions introduce the need for a detailed and consistent analysis of the whole-life carbon emission of HVAC systems, while considering indoor comfort. This study comparatively evaluated the whole-life carbon and energy performance of different HVAC systems in an office building. A thermally activated building system (TABS), and a configuration with active chilled beams (ACB) and wall-mounted radiators, both with a centralized variable air-volume system, were investigated through a life cycle assessment (LCA) framework. Building performance simulations were carried out in IDA ICE 5.0, with indoor environmental quality according to EN 16798-1 Category II; using the operative temperature and the CO2 concentration as indicators, was set as a prerequisite to the LCA. The whole-life carbon emission of TABS was 6.5 kg CO2-eq./m2/year and 6.0 kg CO2-eq./m2/year with heavy and light construction, respectively. Similarly, the emissions with ACB and radiators were 6.5 kg CO2-eq./m2/year and 4.7 kg CO2-eq./m2/year. Embodied carbon emissions were higher with the TABS compared to the configurations with ACB. The primary energy use and thus the operational carbon emissions were lower for configurations utilizing TABS. The embodied carbon emissions from HVAC were a considerable part of the total embodied emissions at 11–17%. The methodology and results are highly relevant for developing a consistent approach for evaluating the environmental impact of buildings and HVAC systems while ensuring indoor environmental quality.