<p>Problematic pornography use (PPU) is a widespread phenomenon in the USA. Recent research suggests PPU to be related to psychological symptoms. Little is known about these associations on a national level and even less about potential interactions with frequencies of pornography use and masturbation. This study utilized a large representative sample (<i>n</i> = 2,773; 53.7% women; 85.1% heterosexual) of US men and women. We tested associations with PPU as well as interaction effects between mental distress (i.e., anxiety and depression), loneliness, and frequencies of pornography use and masturbation. All study variables displayed statistically significant positive correlations with PPU. Interaction effects between loneliness and pornography use frequency (<i>β</i> = 0.10) and between mental distress and masturbation frequency (<i>β</i> = 0.11) in predicting PPU were found. PPU relates to symptoms of anxiety, depression, and loneliness in US men and women. Individuals who experience loneliness with pornography use and mental distress with masturbation may be specifically vulnerable to PPU. Further research is needed to examine these associations and effects in longitudinal designs.</p>