Third seed Dominic Thiem has squandered four match points in a shock second-round loss to Diego Schwartzman at the Montreal Masters.
The world No.7 had battled back from a set down to lead 5-2 in the decider but lost five games in a row against the Argentinian, who prevailed 6-4 6-7 (7-9) 7-5.
In the day's other second-round contest, 20-year-old Jared Donaldson had few problems in overcoming Frenchman Benoit Paire 6-2 7-5.
Donaldson's fellow Americans Jack Sock and Wimbledon semi-finalist Sam Querrey also saw off French opponents, with Querrey requiring three sets to oust Vincent Millot 4-6 7-6 (7-4) 7-5.
Querrey's frustration boiled over early in the third set when he broke his racquet after having his service broken.
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He went on to win the next four games after the outburst.
Querrey goes on to face another Frenchman, Jo-Wilfried Tsonga, the 2014 Rogers Cup champion in the round of 32.
Sock, the 15th seed, beat Pierre-Hugues Herbert 7-6 (7-4) 6-3.
The home crowd had something to celebrate when 18-year-old wildcard Denis Shapovalov overcame a difference of 79 places in the world rankings and saved four match points in his 4-6 7-6 (10-8) 6-4 victory against Rogerio Dutra Silva.
Ninth seed David Goffin came from a set down to beat Yuichi Sugita 4-6 6-1 6-4, while 11th seed Pablo Carreno Busta also came through in three sets against Karen Khachanov.
Paolo Lorenzi saw off Frances Tiafoe in three sets to tee up a second-round meeting with Nick Kyrgios, but world No.28 Feliciano Lopez was shocked by Hyeon Chung, who clinched a deciding tiebreak.
Kevin Anderson, Borna Coric and Ernesto Escobedo also won their openers on Tuesday.
But 10th-seeded Czech Tomas Berdych withdrew from the tournament before his first-round match against Nikoloz Basilashvili.
