Ding, 32, had not won a classical chess match since January and he appeared to be on the defensive early on against his opponent, who played with the white pieces, and took up a great deal of his time allotment to contemplate each move.
But he turned things around with a bold attack by his queen, and put 18-year-old Gukesh on the back foot and also left him facing time pressure.
Ding managed to press home his advantage in masterful fashion and although Gukesh was able to extend the contest, he eventually conceded the game after 42 moves in more than four hours of play.
"For sure I was nervous... it would be surprising if I said I wasn't nervous, I was surely nervous," Gukesh told reporters after the match.
"But after the game started, I calmed down... I think I was playing some good chess... and then I kind of flipped."
Ding, who took a nine-month break from chess last year due to personal difficulties and depression, said he had ample time to prepare for the match since his last classical game two months ago.
Playing the black pieces, Ding said he thought he was at a disadvantage.
"But then suddenly I found this idea... I'd be (able) to create counter-breaks on the queen side, and I just moved the piece very quickly," he said at the after-match news conference.
The result ended a run of 28 classical games without a win for Ding, who had been winless since beating Dutchman Max Warmerdam in January.
Ding and Gukesh will face off for game two at Singapore's Resorts World Sentosa on Tuesday.
At his age, Gukesh is the youngest player in history to challenge for the World Championship and he will hope to surpass Garry Kasparov as the youngest undisputed world chess champion.
There are 14 match days and four rest days scheduled for the world chess crown.
The first player to get 7.5 points will be declared the winner with tie-breaks scheduled if the players are tied on seven points after 14 games.
