Gamma-ray astronomy has been one of the prime scientific research fields of the Max-Planck Institute for Extraterrestrial Physics (MPE) from its beginning. Over the years, the entire gamma-ray energy range accessible from space was explored. The purpose of this review article is to summarise the achievements of the gamma-ray group at MPE during the last 50+ years. This covers a substantial part of the general history of space-based gamma-ray astronomy, for which both, general review articles (e.g. Pinkau in Exp Astron 5: 157, 2009; Schönfelder in AN 323: 524, 2002; Trimble in AIP Conf Proc 304: 40, 1994) and a detailed tabular list of events and missions (Leonard and Gehrels in https://heasarc.gsfc.nasa.gov/docs/history, version 1.0.8, 2009), have been compiled. Here, we describe the gamma-ray activities at MPE from the beginning till the present, reviewing the tight interplay between new technological developments towards new instruments and scientific progress in understanding gamma-ray sources in the sky. This covers (i) the early development of instruments and their tests on half a dozen balloon flights, (ii) the involvement in the most important space missions at the time, i.e. ESA’s COS-B satellite, NASA’s Compton Gamma-ray Observatory and Fermi Space Telescope, as well as ESA’s INTEGRAL observatory, (iii) the participation in several other missions such as TD-1, Solar Maximum Mission, or Ulysses, and (iv) the complementary ground-based optical instruments OPTIMA and GROND to enhance selected science topics (pulsars, gamma-ray bursts). With the gradual running-out of institutional support since 2010, gamma-ray astrophysics as a main research field has now come to an end at MPE.