Movements of male white-tailed deer (Odocoileus virginianus) are of great concern with respect to spread of chronic wasting disease (CWD) across landscapes because most yearlings males disperse and adult males have higher prevalence of CWD than do females and younger deer. We radiocollared and monitored 85 male white-tailed deer in the middle Missouri River Valley of eastern Nebraska and western Iowa, USA from 2004 to 2008. Average size (±SE) of fixed-kernel annual home ranges (95%) and core areas (50%) for resident deer were 449 (±32) ha and 99 (±7) ha, respectively. Resident deer exhibited a high-degree of fidelity to their home ranges. Mean overlap between consecutive annual home ranges and core areas was 81% and 74%, respectively. Average dispersal distance was 17.7 ± 4.5 km (range = 3–121 km) for 22 radio-marked and 6 ear-tagged yearlings. Mean spring dispersal distance (25 km) was 150% greater than fall (10 km). Dispersal direction from Desoto National Wildlife Refuge (DNWR) was bimodal on a northwest to southeast axis that followed the Missouri River corridor. Of 22 yearlings that dispersed 18 (82%) established adult home ranges within the river valley. Dispersal movements of yearling males represent the greatest risk for rapid spread of diseases from infected source populations. Disease management efforts in riparian habitats should target male fawns and yearling males for removal in areas within or immediately adjacent to river corridors.