Shelton won the first clash between the pair, beating the Australian ninth seed 6-3 6-4 in Toronto on Tuesday (Wednesday AEST).
The fourth-seeded American left-hander was pretty much invulnerable on serve, rocketing down 11 aces to just one from de Minaur.
Shelton was also more effective with his return game, converting three of the five break points he set up during the 92-minute match.
De Minaur, who started the contest on an eight-match winning streak, could only take advantage of one of the two break opportunities he was able to muster.
Shelton's victory sets up a clash with second-seeded compatriot Taylor Fritz, who proved too strong for No.6 seed Andrey Rublev, beating the Russian 6-3 7-6 (7-4).
It will be the first all-American semi-final in an ATP Masters 1000 tournament in 15 years.
"A lot of guys see me just as a server and not as a baseliner,'' Shelton said after his win over de Minaur, one of the most nimble, agile and fleet-footed players on the circuit.
"When I get into a match and go into lockdown mode and put a million balls in the court, my rally ball does come with a good bit of weight, and I feel I surprise guys at times.
"Being able to win longer rallies and not feeling like I'm rushing to make something happen is a huge part of my evolution (as a player).''
The other semi on Wednesday (Thursday AEST) will feature top seed and 2017 champion Alexander Zverev, of Germany, up against 11th-seeded Russian Karen Khachanov.
While disappointed with his loss, de Minaur will take encouraging form into the year's final major, the US Open, held on the hard courts in New York from August 24.
De Minaur's efforts in Toronto followed his superb victory in the Washington Open, played on hard courts, where he clinched his 10th career title. The Australian now has a tour-leading 24 hard-court victories for the season.
His string of victories in Washington and Toronto keeps him in line for a top-eight seeding at the US Open, where he is a two-time quarter-finalist (2020, 2024).
Before the US Open, de Minaur will compete at the Cincinnati Open, where he is the sixth seed in a tournament that also includes world No.1 Jannik Sinner and No.2 Carlos Alcaraz.
Meanwhile, fellow Australian Alexei Popyrin is projected to climb inside the world's top 20 for the first time at a career-high No.19 next week.
Popyrin has also hit top form at the right time and will be looking to improve on last year's showing at the US Open.
He reached the fourth round at Flushing Meadows in 2024, hot on the heels of winning his first Masters 1000 title at the Canadian Open.
