In recent years, museums, archives and other cultural institutions have initiated important programs to digitize their collections. Millions of artefacts (paintings, engravings, drawings, ancient photographs) are now represented in digital photographic format. Furthermore, through progress in standardization, a growing portion of these images are now available online, in an easily accessible manner. This thesis studies how such large-scale art history collection can be made searchable using new deep learning approaches for processing and comparing images. It takes as a case study the processing of the photo archive of the Foundation Giorgio Cini, where more than 300'000 images have been digitized. We demonstrate how a generic processing pipeline can reliably extract the visual and textual content of scanned images, opening up ways to efficiently digitize large photo-collections. Then, by leveraging an annotated graph of visual connections, a metric is learnt that allows clustering and searching through artwork reproductions independently of their medium, effectively solving a difficult problem of cross-domain image search. Finally, the thesis studies how a complex Web Interface allows users to perform different searches based on this metric. We also evaluate the process by which users can annotate elements of interest during their navigation to be added to the database, allowing the system to be trained further and give better results. By documenting a complete approach on how to go from a physical photo-archive to a state-of-the-art navigation system, this thesis paves the way for a global search engine across the world's photo archives.