This book constitutes the refereed proceedings of the IFIP TC 5, TC 12, WG 8.4, 8.9, 12.9 International Cross-Domain Conference for Machine Learning and Knowledge Extraction, CD-MAKE 2019, held in Canterbury, UK, in August 2019. The 25 revised full papers presented were carefully reviewed and selected from 45 submissions. The cross-domain integration and appraisal of different fields provides an atmosphere to foster different perspectives and opinions; it will offer a platform for novel ideas and a fresh look on the methodologies to put these ideas into business for the benefit of humanity.