For Del Potro, number three in the world, it was a heartbreaking experience to enter his second Slam final, nine years after he was crowned champion of the US Open.
It was the fifteenth victory of Djokovic over the Argentine and the fifth in five in the Slams.
"I mean Pete, I love you, you're my idol," said Djokovic of Sampras.
"For the support of my loved ones, my children, my wife, my small team of people who have also been with me during difficult times," added the Serbian who underwent elbow surgery after the Australian Open in January. .
For Del Potro, number three in the world, it was a heartbreaking experience to enter his second Slam final, nine years after he was crowned the US Open champion before a long battle with wrist injuries that led to depression and on the verge of retirement.
"When I had my surgery I could really understand what Juan Martin was going through when he had surgeries that kept him away from the tour for two or three years," Djokovic added.
The victory also means that 50 of the last 55 majors have been won by the "Big Four" of Federer, Nadal, Djokovic and Andy Murray.
With the roof of the Arthur Ashe Stadium closed while the heavy rain lashed New York, the conditions were slow and slow.
After taking only two points from Del Potro's first three service games, Djokovic, in his eighth final in New York and 23 in the majors, pounced to break for 5-3.
The key was his success with a rally of 22 shots that shattered the lungs and pocketed the set when Del Potro, 29, scored a forehand.
It was only the second set that fell the Argentine in the tournament.
For Djokovic, it was an illustration of his growth in the championships, as he led his streak of consecutive sets won to 14, going back to the second round against Tennys Sandgren.
Djokovic was early 3-1 up in the second set before Del Potro forged his first break point of the match to tie 3-3.
He had three more chances in the eighth inning, all saved by Djokovic in a marathon 20-minute game that left Hollywood star Meryl Streep in awe.
The effort made a dent in Del Potro suddenly tired as Djokovic claimed a set of 95 minutes in the tie-break.
Del Potro sought to become the first man since Pancho Gonales in 1949 to win the title of EE. UU From two sets down.
Djokovic escaped a 3-1 lead in the third set before a Del Potro stood firm, hitting 3-3.
But after a rally of 24 strokes, Djokovic broke again by 5-3 and was so close to his fourteenth Grand Slam title, just three months after having left Roland Garros in despair after a disastrous exit from the quarterfinals. final. .