The 33-year-old American told a news conference at Flushing Meadows he could have played on but decided it was time for him to quit.
"This is my last tournament," he said. "I have had 14 pretty darn good years on tour, loved every minute of it, and I definitely couldn't have asked for a better career.
"I'm really, really excited I have gotten to do this on my terms. I had knee surgery a couple years ago, and if that had been the end it would have been a little more disappointing to me to end it without going out the way I am now where still just two weeks ago I beat a guy top 20 in the world."
Blake, currently ranked 100th in world, plays Croatia's Ivo Karlovic in the first round of the US Open.
One of the most respected players on the circuit, Blake was inspired to take up tennis after hearing Arthur Ashe address a group of young players at a tennis clinic in Harlem.
He turned professional in 1999 after attending Harvard University but endured plenty of hardship along the way.
He was diagnosed with curvature of the spine when he was a child and broke his neck in a freak accident in Rome in 2004, the same year his father died, but said his experiences gave him a sense of perspective in a sport where players earn millions of dollars and travel the world.
"I think that time being part of the biggest tragedies of my life to this point also clued me in to how lucky I am right now to be doing this on my terms, because my career could have ended twice in 2004. I was millimeters from breaking my neck in the way that would have left me paralyzed for the rest of my life," he said.
"When that happened and I was able to get back in a few months, I knew how lucky I was. Unfortunately, it was also the time my father passed away, and that had an effect on me physically with shingles.
"If I hadn't gotten to the ER immediately for treatment they said my facial nerve could have died. If that's the case, I never would have played.
"(It) easily could have ended right there and my life could have been drastically different. I know how lucky I am to be where I am and to be able to do it this way."
During his career, Blake won 10 ATP singles titles and reached a highest-ranking of fourth in 2006.
He reached the quarter-finals at three grand slams and was a key member of the US team that won the Davis Cup in 2007.
"I have no regrets. Some things are out of my control obviously. If I could do it all over again, if I had, you know, a genie in a bottle and could make one wish, I'd wish my dad was here to see the rest of my career," he said.
"I really hope the mark is just that I did things the right way. I don't kid myself, I know I have had a great career in my eyes, but it's not one that's going to go down in the history books.
"It's not one that's going to end in Newport (Hall of Fame), but it's one that I'm proud of."
- Sports & Recreation