Paul Hambleton Landacre was born in Columbus, OH, on 9 July 1893. He attended Ohio State University where he was a track and field athlete with dreams of participating in the Olympics. During his sophomore year, he contracted a streptococcus infection that caused permanent damage to his right leg and meant the end of his running career. After a long convalescence, he left the midwest for San Diego, where his father and stepmother had settled, and found work as a commercial illustrator at an advertising firm where he met his future wife, copywriter Margaret McCreery. Margaret Gertrude McCreery had been born in Missouri in 1891, but by the early 1910s had also relocated to San Diego with her parents and siblings.

Around 1923, Margaret moved to Los Angeles to further her career, and Paul soon followed. They married in 1925 and settled in the Edendale neighborhood of Los Angeles, in a house on El Moran Avenue where they would live for the rest of their lives. Landacre enrolled in some drawing courses at the Otis Art Institute in Los Angeles, but he largely taught himself the craft of printmaking. In 1929, Margaret introduced Paul and his work to Jake Zeitlin, the Los Angeles bookseller for whom she worked at the time, and Zeitlin became an important early champion of Paul and his artwork. Through Zeitlin, Landacre also met Delmer Daves, another significant supporter and friend. During the 1930s, Landacre produced editions of single prints, in addition to working on book and magazine illustration. He also received some income from the Landacre Association, a subscription scheme organized by Zeitlin and Daves. Increasing commissions for book illustrations drew his attention away from art prints during the 1940s. The most notable books containing his work are California Hills (1931), The Boar and Shibboleth (1933), five books by Donald Culross Peattie (1939-1953), Tales of Soldiers and Civilians (1943), De Rerum Natura (1957), and On the Origin of Species (1963). From 1953 until his death he taught a course at Otis Art Institute.

Over the course of their lives together, Margaret played an instrumental role in Paul's career, continuing to work outside their home in addition to working behind the scenes to organize his business affairs and running their household (which included a succession of bulldogs). In 1963 Margaret McCreery Landacre died of cancer, and four weeks later, Paul Landacre died of injuries sustained in an attempt to take his own life.