After his diploma in 1979, Platzeck worked at the institute for hygiene in Karl-Marx-Stadt (today Chemnitz) in 1979–1980 and the general hospital in Bad Freienwalde from 1980 to 1982.

[2] From February to April 1990 he represented the oppositional radical Green Party as Minister without Portfolio in the last non-elected but legitimate government of the GDR.

In 1998 he was elected mayor of Brandenburg's capital Potsdam and rejected the offer of Chancellor Gerhard Schröder to join the federal cabinet as Minister for Transport.

Both in 2015 and 2016, Platzeck and Bodo Ramelow were appointed as unpaid arbitrators for negotiations between Deutsche Bahn and the German Train Drivers' Union (GDL).

[6] In 2019, Platzeck was appointed by the Federal Ministry of the Interior, Building and Community to chair the committee that oversaw the preparations for the 30th anniversary of German reunification.

[7] In late 2020, Platzeck was appointed as arbitrator in a conflict between Charité and the United Services Trade Union (ver.di);[8] negotiations were successfully concluded by February 2021.

[9] Following her election as Governing Mayor of Berlin in September 2021, Franziska Giffey mandated Platzeck with helping to end a six-weeks long strike of Vivantes Hospital Group employees.

In response, Chancellor Angela Merkel rejected Platzeck's choice of words and argued that reunification was precisely what east Germans had wanted, not a process forced upon them.

His comparison (2016) of the deployment of the Bundeswehr to Lithuania as part of the NATO Enhanced Forward Presence with Operation Barbarossa was also criticized.