Mottl was born in Unter Sankt Veit, today Hietzing, Vienna in 1856. His date of birth has been reported variously as 29 July, 24 August, and 29 August. After early voice training at the Löwenburg Konvikt, a training school for the Imperial Court Chapel, he had a successful career at the Vienna Conservatory. He was soon recognized as a gifted conductor of Wagner's music, assisted Hans Richter in preparing the first complete Ring Cycle at Bayreuth in 1876, and himself conducted Tristan und Isolde at Bayreuth in 1886. From 1881 to 1903 he was chief conductor at the Karlsruhe Opera and was widely renowned for his work there, particularly in Wagner, Berlioz and Chabrier, whose operas he championed. He also orchestrated Chabrier's Bourrée fantasque and Trois valses romantiques, and arranged a popular suite of orchestral excerpts from Christoph Willibald Gluck's operas. In later years, as a conductor of Wagner especially, he visited London and New York, guest-conducting the Metropolitan Opera in 1903. He was made a director of the Akademie der Künste at Berlin in 1904.
In June 1907 he cut some player piano rolls with Welte-Mignon, including his own piano transcription of the Prelude, the Love Duet and Brangäne's Warning from Tristan. He suffered a heart attack on 21 June 1911 while conducting his 100th performance of Tristan in Munich. He was taken to a hospital where he died 11 days later on 2 July, but not before marrying his longtime mistress, the soprano Zdenka Fassbender.