Comparisons in infectivity among the clinically important nontuberculous mycobacterial (NTM) species have not been explored in great depth. Rapid-growing mycobacteria including Mycobacterium abscessus and Mycobacterium porcinum can cause indolent, but progressive lung disease. Slow-growing members of the Mycobacterium avium complex (MAC) are the most common group of NTM to cause lung disease and molecular approaches can now distinguish several distinct species of MAC including Mycobacterium intracellulare, Mycobacterium avium, Mycobacterium marseillense, and Mycobacterium chimaera. Differential infectivity among these NTM species may, in part, account for differences in clinical outcomes and response to treatment; thus, knowing the relative infectivity of particular isolates could increase prognostication accuracy and enhance personalized treatment. Using human macrophages, we investigated infectivity and virulence of nine NTM species as well as multiple isolates of the same species. We also assessed their capacity to evade killing by the antibacterial peptide cathelicidin (LL-37). We discovered that the ability of different NTM species to infect macrophages varied among the species and among isolates of the same species. Our biochemical assays implicate modified phospholipids which may include a phosphatidylinositol or cardiolipin backbone, as candidate antagonists of LL-37 antibacterial activity. The high variation in infectivity and virulence of NTM strains suggests that more detailed microbiological and biochemical characterization is necessary to increase our knowledge of NTM pathogenesis. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).