Honeck made his operatic debut with the Vienna Volksoper in 1989, leading Johann Strauss Jr.'s Die Fledermaus. Later in the season, he was invited to lead the company in Mozart's Le Nozze di Figaro and Rossini's Il Barbiere di Siviglia. In 1990, he was invited to conduct the gala concert of the Vienna Philharmonic commemorating the 75th anniversary of the dedication of the Wiener Konzerthaus. Other conducting opportunities quickly opened up: he led the Berlin State Orchestra, the Berlin State Opera at the Unter den Linden Theater, and the Hamburg State Opera. At the later position, he was again standing in Gustav Mahler's footprints when he led the official Mahler Production of Mozart's Così fan tutte. In 1991, Honeck received a five-year contract with the Zürich Opera House as First Kapellmeister. There he added Massenet's Hérodiade and Giordano's operas Fedora and Andrea Chénier to his credits, and conducted the first performance of Herbert Willi's Schlafes Bruder. A high point of this early part of his career was his debut at Salzburg, conducting the Vienna Philharmonic during the Mozart Week of 1994. In 1996, Honeck became chief conductor of the MDR (Central German Radio) Symphony Orchestra of Leipzig. In 1997, he was appointed music director of the Norwegian National Opera, and in 1998 he was named principal guest conductor of the Oslo Philharmonic. He was chief conductor of the Swedish Radio Symphony Orchestra (2000-2006) and music director of the Staatsoper Stuttgart (2007-2011), and since the 2008-2009 season, he has been music director of the Pittsburgh Symphony. With the Pittsburgh Symphony, Honeck has recorded for Exton Classics and for the orchestra's in-house Reference Recordings label. He has continued to specialize in late Romantic repertory, recording several Mahler symphonies, Bruckner's Symphony No. 4 for Reference in 2015, and suites from Richard Strauss' Elektra and Der Rosenkavalier for the same label the following year. In 2017, Reference Recordings released the Honeck/Pittsburgh recording of Shostakovich's Symphony No. 5 in D minor, Op. 47, powerfully coupled with Barber's Adagio for Strings.
Honeck continues to reside in Austria, in the village of Altach, with his wife, Christiane, and six children.