[2][4] He hoped to follow in the footsteps of his father and started his career from 1860 in church council of Gelderland and he found the job of a preacher not to his liking.

[2] He then wrote a few articles on the value of various hieroglyphics and the numerals in Egyptian in "Zeitschrift fur Aegyptische Sprache und Alterthumskunde" which were well received.

A notable work of Pleyte was in 1868, when he wrote an article for "Etudes Égyptologiques" in which he gave a translation and commentary of the hieratic text on the verso of Papyrus Leiden I 348.

[7] In his last major work Chapitres supplémentaires du Livre des Morts 162–174 (1881–1882), he translated and analyzed different parts of the Book of the Dead.

Starting in 1869, Pleyte applied for the curator position at the "archaeological cabinet" (Rijksmuseum van Oudheden); earlier he had been invited only as a volunteer.

[2] Even though there was opposition from the Director Conradus Leemans, Pleyte appointment as conservator was approved by the Minister on 11 January 1869 and he took charge on 1 February 1869.

[2][4] Before his appointment as curator, he had visited the Museum at Turin where he found that a large number of hieratic papyri were organized scientifically.

Not long after his appointment as director, Pleyte began to suffer from rheumatism and his wife who had a great influence on his life died in 1895.

[2] As one of the leading specialists in hieratic of his time, a portrait bust of Willem Pleyte was included in the funerary monument for Auguste Mariette in the garden of the Egyptian Museum in Cairo.