The 18-year-old, the youngest player in the world top 100, fired an unreturnable serve on match point to take down the 20-year-old Greek -- the youngest player in the top 10.
While the outcome was an upset on paper, Auger-Aliassime held a 3-0 advantage over Tsitsipas when they met as juniors.
"I didn't know what to expect today because he's a completely different player (now)," said Auger-Aliassime after their morning match.
"I believe in myself. I thought I had my chances. I served really well today, so that was obviously a big key."
Next up for last month's Rio Open finalist is Japan's Yoshihito Nishioka, who defeated Spain's Roberto Bautista Agut 7-6(3) 6-4 in a chillier evening session.
World number one Novak Djokovic picked up steam during his second-round match against American Bjorn Fratangelo under the lights on the stadium court as he goes in search of his 74th ATP title.
Djokovic sprinted over to the stands to shake hands with his idol, 14-times Grand Slam champion Pete Sampras, immediately after the 7-6(5) 6-2 win.
"I was a bit nervous, I don't get to see Pete that often," the 31-year-old Serb told reporters.
"It's a thrill to see someone that I looked up to when I was a kid."
A sharp Philipp Kohlschreiber broke Nick Kyrgios twice en route to a 6-4 6-4 win that took just over an hour.
Kohlschreiber deployed a wide variety of shots to keep the 23-year-old Australian guessing and managed to save all five of Kyrgios' break-point opportunities.
American qualifier Marcos Giron battled back to down 23rd seed Alex de Minaur 1-6 6-4 6-2 for the biggest win of his career.
Playing in just his fourth ATP tournament, the Southern Californian settled down after a shaky first set to dispatch the 20-year-old Australian.
Giron, 25, will be a heavy underdog when he faces Canadian 13 seed Milson Raonic, who pounded down 18 aces to send American Sam Querrey packing from Indian Wells for the second consecutive year with a 7-6(1) 6-4 victory.
France's Gael Monfils outlasted Argentina's Leonardo Mayer 6-4 3-6 6-3 under blue skies on the stadium court.
With the win Monfils, who won last month's Rotterdam Open, improved his 2019 record to 13-3.
He will next face Spaniard Albert Ramos Vinolas, who upset 15th-seeded Italian Marco Cecchinato in their second-round meeting.
Seventh seed Dominic Thiem toppled Australian Jordan Thompson 6-4 7-5 to close out the action on Saturday.
The Austrian baseline specialist will next face France's Gilles Simon, who he has defeated in eight of 10 career meetings.
Third seed Alexander Zverev had a stress-free opening match of the tournament, winning 6-3 2-0 over Martin Klizan, who was forced to retire with a right ankle injury in the second set.
India's Prajnesh Gunneswaran, Germany's Jan-Lennard Struff and Serbia's Miomir Kecmanovic were among the other players to advance to the third round.
