Draper earlier this month became the first British man to reach the US Open semi-finals since Andy Murray won the title 12 years ago.
He was looking to build on his success in Tokyo but he needed medical treatment on his upper body late in a first set that Humbert won 7-5.
The Frenchman was leading 2-1 in the second when Draper signalled that he could not continue.
"I feel sorry for him because he was not 100 per cent but at least we played an amazing first set with a great level, great intensity," said Humbert.
"I'm just happy to be in the semis."
Draper had not dropped serve in two matches heading into the quarter-finals in Tokyo but Humbert broke him three times in a hard-fought first set.
Humbert, who is ranked 19th in the world and has won two titles on the ATP tour this year, will face the Czech Republic's Tomas Machac in the semi-finals.
Machac beat American qualifier Alex Michelsen 7-6(2), 6-3 in the day's first quarter-final.
"Everyone is playing so good, the ranking doesn't matter," said Humbert.
"Everyone plays really good, everyone can beat everyone. I just try to take my chance, to play my game, and let's see what happens."