The 21-year-old, currently playing for Seattle Sounders, has completed a medical and will sign an agreement to join Spurs following the end of the current MLS season.
The youngster is believed to have agreed a long-term deal at White Hart Lane and moves for a fee in the region of £2.5million.
Seattle general manager Adrian Hanauer said: "He’s talking to a big club in Europe at the moment.
“We are working towards a potential transaction but we expect DeAndre to be back for our game on Sunday and for the remainder of the season.
“The MLS transfer window won’t impact this deal. This potentially will be a deal where he is not immediately transferred and then loaned back, but constructed in a way that he will be here until the end of the year, or potentially longer.
“For him this is potentially a long-term move, not a short-term one.”
Yedlin impressed at the World Cup as USA reached the knock-out stages and further caught the eye of Tottenham manager Mauricio Pochettino in the 3-3 friendly draw against Seattle earlier this summer.
He has seven caps for the US under former Spurs striker Jurgen Klinsmann and has played 42 times in MLS for Seattle.
The MLS regular season finishes on October 20, when the Sounders face LA Galaxy, before a post-season play-off that concludes with the final in December.
Pochettino has been keen to strengthen defensive positions in the current window, having already signed Wales left-back Ben Davies from Swansea.
Sky Sports also understands Tottenham are continuing talks with Villarreal over Argentine centre-back Mateo Mussachio.
The two clubs opened discussions last week but the deal is complicated due to third-party ownership of the 23-year-old, who can also play at right-back.