Meanwhile, Elina Svitolina defeated Simona Halep in three sets to win the women's title.
And now we have a new supercoach on the tour, stepping into the shoes vacated by Boris Becker at the end of previous year.
Djokovic, who has wrestled with injuries and lack of confidence since winning the French Open last June, had looked his old dominant self when he beat Dominic Thiem in Saturday's semi-final but was unable to recapture that form on Sunday. "If we would get into a rally, he would smash the ball from the first or second shot", said Djokovic. We ll see what future brings. We don't have any long-term commitment. He now begins to work with Agassi this week, and it will be interesting how quickly the American can, if at all, help the 12-time Grand Slam champion, who reportedly also approached Pete Sampras, Pat Rafter, and Gustavo Kuerten about the possibility of coaching him.
Zverev becomes the youngest Masters 1000 victor since a 19-year-old Djokovic won the Miami Open in 2007.
The title means Zverev moves to a career-high No. 10 in the ATP rankings on Monday, placing him firmly in contention at Roland-Garros.
Djokovic continued to struggle for consistency and fell further behind when a missed forehand gave Zverev his second break to go 2-1 ahead in the second set.
After winning his first ATP Masters title and breaking into the top 10 in the rankings for the first time, Zverev said: 'It's something truly wonderful.More news: Blues Musical Legend Gregg Allman Dies at 69
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But Zverev was composed throughout and won in one hour and 21 minutes.
"It's such an honour being on the court against one of the best ever players", Zverev said after his triumph.
"Anybody that knows me, knows that I think he should win everything all the time", Agassi said in July. "Unfortunately this week you didn't win, but I'm sure as we get closer to Paris you'll be one of the favourites for the title".
"You are definitely on a great path", he said. "He understands the game amazingly well".
It was a tour-best fourth title this year for Svitolina and the most prestigious trophy of her young career.
Halep, who won the Madrid Open last week, needed treatment after going over on her right ankle in the second set as she hit a return from the baseline.
But he was outplayed by Zverev who dominated the match after breaking serve in the opening game.
"Sorry guys for third set", Halep told the crowd.