Humber, a top pitching prospect from a Texas high school, attended Rice University, where he had a successful career.

Humber was named 2001 Texas High School Class 4A Player of the Year[1] and enrolled at Rice University for the next season.

On August 22, 2007, he pitched 8+1⁄3 no-hit innings for the Triple-A New Orleans Zephyrs of the Pacific Coast League against the Iowa Cubs.

[6] The Mets traded Humber along with Carlos Gómez, Kevin Mulvey, and Deolis Guerra for two-time Cy Young Award-winning pitcher Johan Santana that offseason.

[8] After pitching for Kansas City for 2010, the Oakland Athletics claimed him on waivers from the Royals, but waived him a week later, at which point he was taken by the Chicago White Sox.

In that contest, Jerry Hairston Jr. broke up the no-hitter leading off the sixth after Roger Bernadina earned a hit by pitch to break up the perfect game in the fourth.

Humber's second start of the season took place on the road in Safeco Field in Seattle, Washington, on April 21, 2012, and was played in front of a crowd of 22,472 people.

The White Sox' catcher was A. J. Pierzynski and Humber's mound opponent, Blake Beavan, was a 2007 Texas high school player of the year.

"[20] Beavan threw a quality start for Seattle, while Humber retired all 27 batters he faced, as his fastball reached 92 miles per hour (148 km/h).

The Fox Sports broadcast never showed any angle which definitively proved whether Ryan had successfully checked his swing, but many fans and media members felt the call was incorrect.

[23] Had Ryan reached first base and no other baserunner been allowed, it would have been the first time in Major League Baseball history that an otherwise perfect game was spoiled by an uncaught third strike.

[27][28] Games between those two rivals generate a great deal of interest and receive extensive media coverage, and are often broadcast on national television.

[34] Humber made an appearance on the Late Show with David Letterman on April 23, where he read the Top Ten List.

[37] The New York Mets, at the time of Humber's perfect game, had never had a no-hitter thrown by a player in the 50-year history of the franchise, though Johan Santana accomplished the feat six weeks later.