La Rue's birth in Tournai cannot be documented because of the destruction of that city's records in World War II, but his early positions of employment have been rediscovered. The earliest record calls him a tenor (adult) at St. Goedele in Brussels in 1469-1470, indicating a birthdate in the early 1450s. The tenor "Pieter vander straten" then proceeded to St. Jacob's in Ghent (during 1471 and 1472) and Onze Lieve Vrouw in Niewpoort (leaving by 1477). He is known to have worked at an unknown church in Cologne at some point, and may have spent some time between 1482 and 1485 at the Cathedral in Siena, Italy. The Italian employment, however, seems questionable on musical grounds, as few traces of Italian styles appear in his music, and no Italian manuscript sources from the time contain any pieces by him. In 1489, at any rate, La Rue began serving a confraternity in 's-Hertogenbosch, from which he would move in 1492 to his "tenured" position with the Hapsburg-Burgundian chapel.
Emperor Maximilian I took La Rue into the chapel he was rebuilding for his son Philip the Fair, Duke of Burgundy (1493-1506). He served Philip throughout his reign, then sang for Philip's widow Juana in Spain until 1508. After this time, La Rue remained in Hapsburg service, as court singer for Marguerite of Austria in Mechlin from 1508 till 1514 and then briefly for the future Emperor Charles V himself. During this service, he seems to have travelled somewhat, meeting Isaac, Févin, and probably Josquin on trips to Spain; Alexander Agricola sang with him in Philip's chapel from 1500-1506. He also continued composition apace; Marguerite held his music in especially high esteem, comissioning two elaborate manuscript volumes of his masses as well as including many of his chansons in her personal chansonniers. After a quarter century of Hapsburg service, La Rue retired to Courtrai in 1516, made his will later that year, and died in 1518. His epitaph lauds his musical service (erroneously read to include Hungary and Ireland), but also commemorates his virtue.