This book constitutes the refereed proceedings of the joint conference on Machine Learning and Knowledge Discovery in Databases: ECML PKDD 2010, held in Barcelona, Spain, in September 2010. The 120 revised full papers presented in three volumes, together with 12 demos (out of 24 submitted demos), were carefully reviewed and selected from 658 paper submissions. In addition, 7 ML and 7 DM papers were distinguished by the program chairs on the basis of their exceptional scientific quality and high impact on the field. The conference intends to provide an international forum for the discussion of the latest high quality research results in all areas related to machine learning and knowledge discovery in databases. A topic widely explored from both ML and DM perspectives was graphs, with motivations ranging from molecular chemistry to social networks.