Though Humber made his major league debut just two years after being drafted, by that point, he had already undergone Tommy John surgery. By the end of 2010, he had passed through the organizations of the Mets, Twins, Royals and A’s, with 51 1/3 innings spread over five seasons, and he was best known for having been included in the 2008 trade that sent Johan Santana from Minnesota to New York. In January 2011, the White Sox plucked him off the waiver wire and he turned in a respectable 3.75 ERA in 163 innings that year while making 26 starts, finishing 9-9.
On April 21, 2012, his second start of the season, Humber shut down the Mariners in Seattle, not allowing a baserunner and striking out nine, the last of which was Brendan Ryan on a controversial check-swing call to end the game. From there, Humber mostly went downhill. He was tagged for nine runs in five innings in his next start, and while he logged four quality starts in May, he posted a 7.39 ERA in his 87 2/3 innings after the gem, notching just four wins and spending a month on the disabled list due to a flexor pronator strain.
Things went even worse after he moved on to the Astros as a waiver-wire pickup in 2013 (0-8, 7.90 in 54 2/3 innings), and by '15, he was getting roughed up in the Korean Baseball Organization. After a last-ditch try with the Padres in the spring of 2016, he retired.