Acicular ferrite nucleates intragranularly on nonmetallic inclusions, forming a microstructure with excellent fracture toughness. The formation of acicular ferrite is strongly affected by the size, content, and composition of nonmetallic inclusions, but also by the composition of the steel matrix. The potential of inclusions in medium carbon HSLA (high-strength low-alloyed) steels has been the main focus in the literature so far. The current study evaluates the acicular ferrite capability of various inclusions types in four different steel grades with carbon contents varying between 0.04 and 0.65 wt pct. The investigated steels are produced by melting experiments on a laboratory scale and subsequent heat treatment in a High-Temperature Laser Scanning Confocal Microscope. Inclusions are exclusively formed by deoxidation and desulfurization reactions. No synthetic particles are added to the melt. The inclusion landscape is analyzed by Scanning Electron Microscopy. Final ductility of the samples is evaluated based on performed tensile tests. Inclusion types in every steel grade are assessed regarding their nucleation potential always considering the interaction with the steel composition, especially focusing on the role of manganese. The effects of (Ti,Al)Ox-, MnS-, and MgO-containing inclusions are discussed in detail.