The California Channel Islands are unique relative to other island chains due to their close proximity to the California mainland and the fact that individual islands, or groups of islands, vary in their distance to the mainland and other islands. This orientation raises questions about whether island taxa with widespread distributions form cohesive evolutionary units, or if they are actually composed of several distinct evolutionary entities, either derived from independent mainland-to-island colonization events or divergence due to prolonged allopatric isolation. The 4 northern islands are clustered in a line (6–8 km separation among islands), while the 4 southern islands are widely spaced (34–45 km separation among islands), which should impact the amount of gene flow and genetic connectivity among islands. We used nuclear microsatellite markers to examine the genetic structure and cohesion of 2 island shrubs, Acmispon dendroideus and A. argophyllus, which are widely distributed across the California Channel Islands. Both focal species contain varieties with multi-island distributions, with A. dendroideus exhibiting a greater distribution on the northern islands and A. argophyllus exhibiting a greater distribution on the southern islands. Substantial genetic divergence was observed for 2 single-island endemic varieties, A. dendroideus var. traskiae and A. agrophyllus var. niveus, confirming that allopatric isolation can lead to genetic divergence. The widespread Acmispon dendroideus var. dendroideus and single-island endemic A. dendroideus var. veatchii formed a cohesive evolutionary group that spans all 4 northern islands and 1 southern island, Santa Catalina, indicating that the northern and southern islands have been genetically linked in the past but do not display evidence of contemporary gene flow. In contrast, widespread A. argophyllus var. argenteus was composed of moderately distinct genetic groups on each of the 4 southern islands, with no evidence of recent gene flow among islands. These results demonstrate that isolation among islands has led to significant divergence among the southern islands, but that the commonly recognized split between northern and southern islands does not impact all taxa equally.