The match ended with Hugo Gaston recording an unlikely victory over Alex de Minaur by a score-line of 4-6, 6-2, 6-3, 0-6, 7-6 (10-4).
The Norwegian Ruud came out as the victor after what was a thrilling contest that saw a brilliant tie-break in the very first set.
Day six saw third seed Rafael Nadal eliminated by Canada's Denis Shapovalov who recorded a fantastic comeback win.
He broke into the top 50 with a career-high ranking of 48. In 2021, he advanced to the Kitzbuhel semi-finals, reached six other ATP Tour quarter-finals.
Tiafoe made his pro debut in 2015, finishing the year as world No. 180 and the youngest guy in the ATP Top 200 rankings.
Busta participated in his first-ever grand slam tournament when he was a qualifier at the 2013 French Open.
While the Canadian has not won a grand slam so far, he is the first player from the nation to reach the quarter-finals of the US Open.
At 17 years and one month, he is the second-youngest player to win multiple Challenger titles, and also is the youngest player to defend one.
Denis Shapovalov is a player many believe is destined to for big things in tennis. Read about the tennis racquet he uses here.
The 22-year-old, who dropped just eight points on serve in eight service games, registered a comfortable 6-4, 6-0 win over the World No. 73 Slovak in just 52 minutes.