The fourth seed played some stunning tennis to beat his opponent from the Russian Olympic Committee 6-1 6-3.
Zverev applied pressure from the start and rarely allowed Khachanov to settle, winning in just an hour and 19 minutes at the Ariake Tennis Park on Sunday.
The 24-year-old had beaten world number one Novak Djokovic to reach the final.
Zverev is yet to win a Grand Slam, but the world number five can now add Olympic gold to his list of 2021 achievements, which include the Mexican Open title and the ATP Masters 1000 crown.
“From beginning to the end, he played an unbelievable match,” said silver medallist Khachanov, 25.
Doubles delight for Czech Republic
Czech Republic pair Barbora Krejcikova and Katerina Siniakova produced a superb performance to win women’s doubles gold.
The top seeds beat Switzerland’s Belinda Bencic and Viktorija Golubic 7-5 6-1.
The win denied Bencic a second gold of the Games after she won the women’s singles title on Saturday.
They become the first Czech Olympic gold medallists in tennis as an independent nation since the split in 1993.
The French Open champions battled through a close first set, but then showed their dominance as a partnership in the second.
Krejcikova’s former coach Jana Novotna, who died at the age of 49 in 2017, was the last Czech tennis medallist, having won bronze at Atlanta 1996.
The bronze medal had been decided on Saturday, with Brazilian pair Laura Pigossi and Luisa Stefani completing the podium.