The year 1581 in art involved some significant events and new works.
- September 19 – Arnold Bronckhorst is appointed first court painter to James VI of Scotland.
- Construction of the Uffizi in Florence as magistrates' offices, designed by Giorgio Vasari and continued by Alfonso Parigi the Elder and Bernardo Buontalenti, is completed.
- Anonymous – Portrait of Dorothy and Penelope Devereux (approximate date)
- Antonio Campi – The Martyrdom of St. Lawrence (San Paolo Converso, Milan)
- Lavinia Fontana
- Noli me tangere
- Nicholas Hilliard – Portrait miniature of Sir Francis Drake
- October 21 – Domenico Zampieri, Baroque Italian painter (died 1641)
- December 27 - Jean Chalette, French miniature and portrait painter (died 1643)
- date unknown
- Johan Bara, Dutch painter, designer and engraver (died 1634)
- Frans Francken the Younger, Flemish painter (died 1642)
- Cornelis Liefrinck, Dutch painter (died 1652)
- Abraham Matthijs, Flemish Baroque painter (died 1649)
- Panfilo Nuvolone, Italian Mannerist painter (died 1651)
- Carlo Sellitto, Italian Caravaggisti painter (died 1614)
- Artus Wolffort, Flemish painter (died 1641)