Auger-Aliassime, 18, becomes the youngest player in 20 years to reach the semifinals of the tournament and was assured in his victory, serving seven aces. He claimed the match's first break of serve in the final game of the opening set before he broke Tsitsipas -- who required treatment on his shoulder midway through the second set -- a further two times in the second.
"I had zero expectations coming here, but I've managed to handle my nerves and keep my serve all the time," No. 8 seed Auger-Aliassime said.
Auger-Aliassime, who reached the final of the Mercedes Cup on grass in Stuttgart last week, is yet to win a title since turning professional in 2017 but is at a career-high ranking of 21.
The 19-year age differential between Lopez (37) and Auger-Aliassime will be the greatest in an ATP Tour semifinal or final since the 43-year-old Ken Rosewall defeated 23-year-old American Pat Dupre to reach the Hong Kong Grand Prix final in 1977.
In the other side of the draw, fourth seed Daniil Medvedev became the first Russian to reach the semifinals of the tournament in the professional era, as he had too much firepower for Argentina's Diego Schwartzman in winning 6-2, 6-2.
Andy Murray's comeback after a five-month absence will continue into the weekend after his doubles match at Queen's Club was suspended in the second set due to darkness on Friday.
The three-time Grand Slam champion and the busy Lopez won their first set 6-4 and were 5-4 down in the second to British duo Daniel Evans and Ken Skupski when fading light forced a halt to play at the grass-court event.
Murray was playing freely in his second match since undergoing what he hopes was career-saving hip surgery 144 days ago.
Information from Reuters and The Associated Press contributed to this report.