Sabalenka, who arrived in Montreal with a chance to claim the number one spot from Iga Swiatek, showed plenty of fight in the nearly three-hour centre court battle but won only two of 13 break points while making 11 double faults, many at key moments.
Samsonova got two breaks from six chances which helped the 15th-seeded Russian into the last eight where she met Swiss Belinda Bencic and progressed to the semi-finals.
Both players will have little time to savour the upsets with their quarter-final set for later on Friday.
"Honestly it is going to be difficult, it's going to be hard. I'll try to save all the energy I can," said Samsonova, who has just two wins over top-five ranked opponents - both against Belarusian Sabalenka.
Sabalenka, winner of three titles this season including the Australian Open, blasted 13 aces but more than offset those with double faults, and one gave Samsonova the decisive break to move 5-3 ahead in the third, allowing her to serve out the match.
"Last year I played unbelievable in the States in general and this year I'm going crazy," said Samsonova, who opened the North American hardcourt season last week with a run to the semis in Washington.
Later on Friday, world number three Pegula kept her nerve against her frequent doubles partner Gauff, saving five of eight break points, and will meet either Poland's world number one Swiatek or fellow American Danielle Collins in the next round.
Pegula confidently marched through the first set but her serve lost its potency and Gauff kept the game alive when she converted a break point in the final game of the second set.
Pegula got back on track when she broke Gauff in the third game of the third set but let the world number seven convert a break point when she whacked a backhand into the net in the eighth game.
"Always a tough match," Pegula told reporters. "We know each other's games so well, so we kind of know what we're going to do to each other, know what our goal is."
Fresh off the biggest win of her career in Washington, Gauff was unable to keep the momentum on her side as she handed Pegula the break and lead in the penultimate game with a double fault, one of nine across the match.
Pegula, who lost in straight sets in their previous meeting in Eastbourne earlier this year, sealed the match with an ace before greeting her friend at the net.
Next up for Pegula is world number one Iga Swiatek, who battled past American Danielle Collins 6-3 4-6 6-2 in the evening session.
Swiatek raced out to a 3-0 lead in the opener but Collins broke back late in the set and carried that momentum into the second, which the tournament qualifier went on to level when Swiatek misfired on set point.
Swiatek regrouped to go on the attack again in the third, breaking Collins for a 2-1 lead and the best front-runner in the game rode that advantage to notch her 50th win of the season.
"I really wanted to play powerful and I'm pretty happy that I managed to even increase the power in the third set," Swiatek said
"For sure, I was looking for that. Today I felt like I really needed to go even higher in terms of the intensity.
"I'm really proud of myself that I made it to the semis. I'm happy that I can play another match."
Third seed Elena Rybakina saved a matchpoint against Daria Kasatkina in a marathon encounter that she won 5-7 7-5 7-6(8) shortly before the clock struck 3 a.m.
"I've played three sets, tough battles, but like this, honestly, physically it's really tough," said Rybakina, who fought hard for three hours and 27 minutes and booked an encounter with Samsonova.
"It's so late, I've never played this late. Thank you so much, and hopefully somehow I can recover for tomorrow."
