He grew up in Chicago in affluent circumstances and studied first at the University of Cincinnati - College-Conservatory of Music, from 1885 at the Hoch Conservatory in Frankfurt piano and violin with Clara Schumann, Hugo Heermann, Bernhard Scholz, Iwan Knorr and Engelbert Humperdinck.
[3][4][5] In 1903, he founded the Wetzler Symphony Orchestra with donations, at which Richard Strauss made his US conducting debut in 1904[3] and premiered his Sinfonia Domestica.
[6][7] In 1905 Wetzler returned to Germany to work as a Kapellmeister in Hamburg, Elberfeld, Riga, Halle, Lübeck and Cologne.
He wrote major works for orchestra from 1917 and finally also the opera The Basque Venus based on a libretto by his wife Lini Wetzler née Dienstbach (1876–1933).
His estate has been in the Zentralbibliothek Zürich since 2006 and contains, in addition to music autographs and writings, around 10,000 letters, 6000 reviews and photographs.