The two leaders will address the European parliament with the aim of presenting a united front on issues such as the refugee crisis, conflict in Ukraine and the future of the EU.
The idea of the leaders of France and Germany speaking to MEPs was first put forward by Martin Schulz, the president of the parliament, back in January.
This initial plan was for them to defend liberty and freedom of speech following the Charlie Hebdo massacre in Paris.
But times have moved on since then and after the Greek crisis and the ongoing influx of refugees, Hollande and Merkel have more pressing problems to address.
They will address the challenges facing the European Union, which have altered dramatically since their predecessors Helmut Kohl and François Mitterrand last made a joint appearance in Strasbourg in November 1989.
Each leader will speak for 15 minutes and then listen and respond to questions from the leaders of the main political groups, including anti-EU groups like Marine Le Pen's National Front and Britain's Ukip party.
"This is a historic visit for historically difficult times. The EU is facing immense challenges and requires strong commitment by its leaders," Schulz said in a statement announcing the visit.
"It is an important signal that such commitment will be made in front of Europe's democratically elected representatives," added Schulz.
Merkel and Hollande, the leaders of the European Union's two biggest economies, have played a leading role in a series of challenges that have gripped the 28-nation bloc, ranging from the migrant crisis to the Greek debt saga and the conflict in Ukraine.