He began photographing his own ideas for covers and soon established himself as a fashion photographer. In 1950 he married model Lisa Fonssagrives, whom he photographed for much of his best work. His austere fashion images communicated elegance and luxury through compositional refinement and clarity of line rather than through the use of elaborate props and backdrops.

Penn also became an influential portraitist. He photographed a large number of celebrities, engaging each subject to sit for hours and to reveal his or her personality to the camera. In his portraits the subject is usually posed before a bare backdrop and photographed in natural northern light. The resulting images combine simplicity and directness with great formal sophistication. A memorable series of portraits he created in 1950–51, collectively called Small Trades, was of labourers in New York, Paris, and London formally posed in their work clothes and holding the tools of their trade.