Microplastics are commonly found in aquatic ecosystems and can pose environmental threats to aquatic organisms. While the threats of microplastic ubiquity are recognized, few studies have concomitantly quantified microplastic abundance and heavy metals along a rural–urban river continuum. In the current study, we studied changes in microplastics and heavy metals (using lead as a proxy) by collecting sediment and water samples along a rural–urban river over two seasons (temperate spring and summer) and across five sites in a North American River. Our results revealed that microplastics decreased in a downstream direction in surface water but did not change predictably in sediment samples collected along the river continuum. Regarding the relationship between microplastic abundance and lead concentrations, we found a positive relationship between microplastics in sediment samples and lead concentrations. Contrariwise, we found no discernible correlation between microplastics in surface water and lead concentrations along the river continuum. Given the presence of microplastics at every site and moderate lead pollution documented in the Wolf River, our results provide baseline data that can aid in the concurrent assessment of microplastics and heavy metals in river systems. These findings can inform environmental managers in planning pollution management strategies for waterways flowing through rural–urban areas.