World number 31 Kohlschreiber was on fire early, ripping through the first set in only 21 minutes but fifth seed Nadal flipped the switch and turned the match on its head to prevail 0-6 6-2 6-3 on the main stadium hard court at Crandon Park.
It was the first time Nadal had failed to win a game in the first set of an ATP tour match since 2008, the ATP said.
The 30-year-old Spaniard ignited the near-capacity crowd with a typically determined comeback to clinch his 822nd career victory.
He joins a small group of 11 players headed by Jimmy Connors (1,535) to have played at least 1,000 matches.
"One thousand matches is a lot of matches. Obviously, that's good news because that says I am having a long career," Nadal told reporters.
"During a lot of years, I heard that I'm going to have a short career, so it's something important for me. I remember the first match very well because it was at home in Mallorca. It was my first victory on the ATP and was a great feeling."
Nadal said he had not done much wrong in the first set against an opponent who was in the zone.
"He was doing everything good, so that's sport. I lose the set because he was playing too good. That's it.
"But a match is long and the positive thing is I held the pressure well this afternoon after a very tough first set. I resisted well in the first few games of the second set and then I think I played a great second and third set."
