In the eighties and early nineties, Lengauer's research concentrated on discrete optimization methods for the design of integrated circuits and on packing problems in manufacturing.

Since 2001, he has been a Director of the Department on Computational Biology and Applied Algorithmics at the Max Planck Institute for Informatics.

On the latter topic he cofounded the company BioSolveIT GmbH in Sankt Augustin, Germany, together with Christian Lemmen, Matthias Rarey, and Ralf Zimmer from his team at GMD.

[6] Since 2000 he and his team have developed methods for analysis of viral resistance of HIV; in 2005 he entered the field of computational epigenetics.

He was a member of the steering committee of the International Conference on Research in Computational Biology (RECOMB) from its inception in 1997 until 2010.

Lengauer has also been a member of acatech, the German Academy of Science and Engineering, since 2007 and of Academia Europaea since 2010.