As cancer strategies shift toward immunotherapy, the need for new binding ligands to target and isolate specific immune cell populations has soared. Based on prior work identifying a peptide specific for murine M2-like macrophages, we sought to identify an aptamer that could bind human M2-like macrophages. Tumor-associated macrophages (TAMs) adopt an M2-like phenotype and support tumor progression and dissemination. Here, we employed cell-SELEX to identify an aptamer ligand that targets this cell population over tissue resident (M0-like) or tumoricidal (M1-like) macrophages. Instead, we identified an aptamer that binds both human M0- and M2-like macrophages and monocytes, with highest binding affinity to M2-like macrophage (Kd ∼ 20 nM) and monocytes (Kd ∼ 45 nM) and minimal binding to other leukocytes. The aptamer binds to CD14+ but not CD16+ monocytes, and is rapidly internalized by these cells. We also demonstrate that this aptamer is able to bind human monocytes when both are administered in vivo to mice. Thus, binding to these cell populations (monocytes, M0-like and M2-like macrophages), this aptamer lends itself toward monocyte-specific applications, such as monocyte-targeted drug delivery or column selection.