The world number 12 is among the leading American hopes of ending a 23-year wait for a home men’s champion in New York and did his part to keep that dream alive, feeding off a partisan crowd at Louis Armstrong Stadium.
The 28-year-old broke Sakamoto in the opening game of the match and held firm to take the set.
He appeared on course to close out the second but consecutive double faults opened the door for Sakamoto, who found another gear and took the set to a tiebreak.
Tiafoe, a twice U.S. Open semi-finalist, regrouped and won four of the first five points in the tiebreak to move two sets ahead.
Sakamoto, who reached the main draw by beating his idol, former U.S. Open finalist Kei Nishikori, showcased his powerful serve, striking 18 aces, but racked up 40 unforced errors.
Tiafoe was relieved to close out the win in straight sets after being taken to five in the first round. He next faces either Kamil Majchrzak or Valentin Vacherot.
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