Tiafoe, 24, is the youngest American to reach this far at the US Open since then 24-year-old Andy Roddick reached the final in 2006.
“It was definitely a great game,” he said following the match. “I played really well today. Yeah, I think, I mean, I just went out there and I believed I could do it. It helps that I played him a couple of times.”
Earlier in the tournament, Tiafoe said he was happy not to be seen often.
After his victory on Monday, he expressed his joy at what his victory over Nadal meant to his parents, who immigrated to the United States from Sierra Leone.
“I had a lot of passion for that game. Not even for me, but to do it for them. Seeing the experience of beating Rafa Nadal, they’ve seen me win big, but to beat those guys Mount Rushmore, for them, I can’t imagine what was going through their heads theirs.
“Yeah, I mean, they’ll remember today for the rest of their lives.”
Nadal, 36, recorded his first loss at a grand slam this year and is now 22-1 on the season. The Spaniard won the Australian Open and the French Open before pulling out of Wimbledon in July ahead of his semi-final clash with Australia’s Nick Kyrgios.
“The difference is simple,” Nadal said later. “I played a bad match and he played a good match. That’s it in the end, no?”
Nadal said Tiafoe played more consistently than in previous matches between the two, served well, had good forehands and was quick.
“But I don’t think I pushed him enough to create the suspense that I need to create,” he said. “Of course, he did things well. If not, he won’t win, of course. Congratulations to him.”
Nadal said he needs to “fix things” and when he feels mentally ready to compete again, he will do so, but is unsure about the timetable.
Tiafoe will face Russia’s Andrey Rublev in the quarter-finals on Wednesday.
The US Open men’s final is scheduled for Sunday.
Tiafoe’s parents met in the United States, where they would give birth to twins, Franklin and Frances.
Their father signed on as a day laborer at the Junior Tennis Champions Center in 1999 in College Park.
As he worked around the clock, his father had to move into an empty room at the tennis center, where his two boys would stay with him, sleeping there, while their mother worked night shifts as a nurse. Tiafoe started the game, playing free center, and he loved it.
Tiafoe previously said that although his family did not become rich, he would not change a thing.
On Monday he told reporters: “Being around tennis was getting us out of our neighborhood. My dad was able to watch us. It wasn’t supposed to be like this. Once we got into the tennis game, it was like my dad, It would be nice if you guys you can use this as a full scholarship to school. I mean, we couldn’t afford college.”
CNN’s Jill Martin contributed to this report.