Seiler worked as a research assistant at the Institute of Meteorology, University of Mainz (1967-1969) and was head of the research group "trace gases" at the Max Planck Institute for Chemistry (MPI), Mainz (1969-1986). In 1978 he was a researcher at the National Center for Atmospheric Research (NCAR), in Boulder, Colorado, where he collaborated with Paul J. Crutzen and Ralph J. Cicerone. In 2001 Seiler was a Highly Cited Researcher (one of world's leading researchers) in the category Geosciences and Ecology/Environment.
From 1986 to 2001, Seiler was the Director of the Fraunhofer Institute for Atmospheric Environmental Research, and from 2001 to September 2007 the Director of Institute of Meteorology and Atmospheric Environmental Research (IMK-IFU) of the Forschungszentrum Karlsruhe (now Karlsruhe Institute of Technology). After he retired, Professor Seiler became an environmental officer (voluntary) of the City of Garmisch-Partenkirchen. Together with Ralf Klemens Stappen he served project leader of the pilot project Sustainable Garmisch-Partenkirchen (Munich 2018, Bid for the 2018 Winter Olympics) and Executive of the Energiewende Oberland.