He debuted for the Twins in 2007 pitching for the Gulf Coast League Twins. He led the team in strikeouts with 52. He was also named as a Twins Top 50 prospect. He pitched for the Perth Heat in the 2008 Claxton Shield and went 3–0 with a 1.90 ERA and 25 K's, a competition high. Liam was then added to the Australian national team for the 2008 Final Olympic Qualification Tournament pitching five innings of work while only allowing one unearned run alongside two hits and a walk while striking out six. Hendriks underwent back surgery that prevented him from playing in the minors in the 2008 season, but made the 2009 World Baseball Classic roster, the youngest Australian player in the Classic.
In 2009 Hendriks spent the season with the Class-A Beloit Snappers of the Midwest League and the Rookie-Level Elizabethton Twins of the Appalachian League. He went a combined 5–5 with a 3.55 ERA in 14 games, all starts. In 2010, Hendriks was selected for the 2010 All-Star Futures Game, but developed appendicitis and was forced to miss the game. On 5 September 2011, Hendriks was called up to the Minnesota Twins from Triple-A Rochester. He went on to finish the season with an 0–2 record. At the end of the 2011 season he was named the Minnesota Twins' Minor League Pitcher of the Year.
After a successful spring training (3–1, 2.84 ERA, 8 games/4 starts), Hendriks was named as one of the Twins' starting pitchers for 2012. On 19 September 2012, Hendriks earned his first Major League victory in a 6–4 win against the Cleveland Indians. On 5 December 2013, the Twins designated Hendriks for assignment, after the signing of pitcher Phil Hughes.
On 13 December 2013, Hendriks was claimed off waivers by the Chicago Cubs. Ten days later, he was claimed off waivers again, this time by the Baltimore Orioles. The Orioles designated him for assignment on 19 February 2014 to make room for Ubaldo Jiménez on the active roster. The Toronto Blue Jays claimed Hendriks off waivers on 21 February 2014. On 10 March 2014, he was optioned to the Triple-A Buffalo Bisons. Hendriks compiled a 5–0 record with an ERA of 1.46 through nine games (seven starts) with the Bisons, before being called-up to the Majors on 23 May 2014. He made his Blue Jays debut that day, picking up a 3–2 win over the Oakland Athletics. Hendriks started the game and allowed 3 hits, 1 earned run, 3 walks and struck out 3 over 52⁄3 innings. After 2 starts for the Blue Jays, Hendriks was optioned back to Triple-A Buffalo on 1 June 2014. He posted a 1–0 record with a 2.31 ERA and 8 strikeouts in his 2 starts. Hendriks was called up on 20 June to start against the Cincinnati Reds, and was sent back down to Buffalo the following day after he pitched only 12⁄3 innings and surrendered 6 earned runs. Hendriks was named as the starter for the International League in the Triple-A All-Star Game after posting a 7–1 record with a 2.19 ERA in 16 starts. In being named the starter, he became only the fourth pitcher from the Bisons to start the All-Star Game.
He pitched for the Perth Heat in the 2008 Claxton Shield and went 3–0 with a 1.90 ERA and 25 K's, a competition high. Liam was then added to the Australian national team for the 2008 Final Olympic Qualification Tournament pitching five innings of work while only allowing one unearned run alongside two hits and a walk while striking out six.