Since creation of the CfA in 1973, most staff members have been headquartered in Cambridge, Massachusetts. However, sites in Arizona and Hawaii, which house SAO's major ground-based observational facilities, are also primary locations for CfA staff.

For nearly 400 years, astronomers have used ground-based optical telescopes to explore the universe. Since the 1930s, radio antennas have captured light from celestial sources. The CfA currently operates telescopes in Arizona and Hawaii and is a partner in facilities in Chile. CfA is also a partner in the GMT consortium, a project to build the world's largest optical/infrared telescope.

Space observatories enable astronomers to observe ancient light unimpeded by the Earth's atmosphere. Aside from providing a clearer view at optical and infrared wavelengths, these instruments allow observations at X-ray and ultraviolet wavelengths where the atmosphere is opaque. In addition to constructing satellite instrumentation for studying the Sun, CfA scientists and engineers designed and built major instruments for the Chandra and Spitzer satellites. Today, several groups are studying approaches for the next generation of space observatories.

Facilities that serve the scientific community by hosting workshops and seminars and by providing opportunities for visiting scientists to conduct or participate in collaborative research are also located at CfA in Cambridge. Among them are the Institute for Theoretical Atomic, Molecular and Optical Physics (ITAMP), the Institute for Theory and Computation (ITC), and the Center for X-ray Technology (CXT).

The CfA provides technical support and resources for the scientific staff, which include engineering, IT support, library and model shop services.