This rare surname is derived from the name of a male ancestor – Padarn, a Welsh forename meaning 'fatherly', adopted from the Latin, Paternus. The 'Up-' prefix gives this surname as undoubtedly Welsh.

Before surnames were common in Wales, men were known by a patronym, e.g. Jevan ap Padarn. In this case the patronym refers to Jevan, son of Padarn. While the majority of Welsh patronyms were adapted into surnames not including the 'ap' or 'ab' prefix, e.g 'ap John' to 'Jones', some included the prefix, e.g. 'ap Richard' to 'Prichard'. In fewer cases still, due to regional differences in accents, patronyms were rendered as 'up' instead of 'ap'. Examples include Uprichard and Upjohn. These cases probably arose when Welsh migrated to areas where there was no knowledge of Welsh patronymics and clergy or other officials essentially gave them a surname as they heard it.

Padarn is the name of a number of historical and legendary Welsh figures, including: St. Padarn, an associate of St. David, patron saint of Wales and Padarn Beisrudd, a Welsh ruler in Scotland.

• 1584. GRANT of a seat and kneeling place in the parish church of Oswestry against the chancel there called our Ladyes Chauncell and adjoining the seat of Richard ap John ap Thomas ap Padarn: Aston Hall Deeds, 2538
• 1678. John Uppadine and Elizabeth Peat, married, St. Matthew's, Walsall