Worked for Ferdinand Weber (1772–82), succeeding him as the leading harpsichord and, later, piano maker in Ireland.

William Southwell is listed in the Dublin Directories as 'harpsichord maker' from 1783 and as 'harpsichord and piano maker' from 1793. Debenham & Geoghegan state that Southwell 'published music and imported, repaired and tuned instruments'.

The earliest Dublin pianos were made by William Southwell (Hogan). He is particularly associated with the development of the Cabinet or Upright Piano. He advertised a 'grand organised pianoforte' in the Freeman's Journal of May 1792, declaring it to be 'superior to the small pianoforte in expression, sweetness and delicacy' (Hogan). His 'new patent Sonovent pianos' were sold in Cork by James Haly, James Roche and William Lewis in 1795 and 1796 (O'Regan).

According to Bozarth, Debenham & Cripps (citing FitzGerald and Peill), William Moore made the cases for Southwell's pianos of the demi-lune type.

In 1804 William drew up a deed of partnership with his brother Nicholas and sons John (ii) and Francis, after which the business was known as 'William Southwell & Co.'. John managed the Dublin shop, Nicholas managed the Liverpool business and William worked in London (Bozarth, Debenham & Cripps). The partnership was due to last four years but was not dissolved until 1814 (Bozarth, Debenham & Cripps) or 1815 (De Valera, 'Two Eighteenth-Century Musical Instrument Makers'). According to De Valera, the partnership was 'to free himself [William] from the day-to-day pressure of general business and to concentrate purely on the design, development and manufacture of instruments and, in particular [...] the piano, but Bozarth, Debenham & Cripps state that the partnership was to protect Southwell from personal loss in defending his patent in court. After William's death in 1825, Nicholas continued the Liverpool business, and John continued the music shop in Dublin (Bozarth, Debenham & Cripps).

[Dates and addresses differ according to sources: Debenham & Geoghegan give 26 Fleet Street from January 1781; 70 Marlborough Street in 1786; and 86 Marlborough Street in 1792. Bozarth, Debenham & Cripps state that Southwell launched his business in 1783. The Dublin Directories give 26 Fleet Street from 1782–86, 70 Marlborough Street from 1787–92, 86 Marlborough Street from 1793–1804 and 34 Marlborough Street from 1804–15. The 77 Marlborough Street address was printed in the Dublin Evening Post and may be a misprint for 70. Teahan gives the 26 Fleet Street address from 1783 to 1786, 70 'Marlboro St' from 1787 to 1792 and 86 'Marlboro St' from 1793 to 1802. Hogan gives the 26 Fleet Street address from c. 1783 to 1786, 70 Marlborough Street from c. 1787 to 1792 and 86 Marlborough Street from c. 1793 to 1803. De Valera ('Two Eighteenth-Century Musical Instrument Makers') gives 26 Fleet Street in 1782, 20 Marlborough Street in 1792 and 86 Marlborough Street from 1793 to 1804. DeValera gives the dates of William Southwell & Co from 1804 until 1815, but Bozarth, Debenham & Cripps give it until 1814 (citing Wilson's Dublin Directory. Flood states that Southwell left Dublin c. 1794, returned in 1836, died in Rathmines in 1842 and is buried in Glasnevin Cemetery. ]