Bacterial engagement of specific host tissue structures can be a means of targeting a pathogen to a particular niche, establishing persistent infections and inducing invasion. In this context, primary adhesion is often the first crucial colonization step allowing pathogens to withstand the mechanical clearing mechanisms of the host. As a consequence, bacteria have evolved adhesins with the capacity to mediate interaction between microorganism and host. Here we describe collagen VI as a novel target for adherence of <i>Streptococcus</i><i>pyogenes</i> and <i>Streptococcus pneumoniae</i>. In upper and lower airways this collagen was distributed in the lamina propria underneath the epithelial basement membrane. Both pathogens exhibited strong affinity to collagen VI as shown by light and electron microscopy in combination with immunodetection and in vitro binding assays. For <i>S. pyogenes</i> this interaction was mediated by M1 protein. The presented data provide evidence for a previously unrecognized role for collagen VI in host-pathogen interplay during respiratory tract infection.