Two sets to one up against the world No.1, a career-best victory beckoned.
Then Sinner regrouped, put Paris to the back of his mind, and raised his game beyond the Serbian journeyman's reach.
After losing a titanic 70-minute third set, Sinner wrapped up the fourth and fifth in 67 combined to win 4-6 6-3 6-7 (6-8) 6-2 6-3.
Which means Lleyton Hewitt remains the last Wimbledon men's champion dethroned in the first round of his defence and the only one since the Open era began in 1968.
The Australian lost to Ivo Karlovic, who went on to become a top-20 player, but in 2003 was an unheralded grand slam debutant.
Kecmanovic, 26, is much more established, has reached No.27 in the world and is currently ranked 50th. So Sinner had reason to fear at 2-1 down, especially given his poor five-set record.
In his 12 previous matches against top-50 ranked opponents to go the distance he had won two.
There was also the spectre of his last match, the second-round defeat on clay at Roland Garros when he lost to Juan Manuel Cerundolo after being two sets and 5-1 up.
"I was a little tight in the beginning, I didn't play my very best," said the Italian, admitting to "a lot of nerves" at opening up on Centre with the added responsibility of defending champion.
"I made a lot of mistakes on the forehand side, but it's normal, first-round matches are never easy. The third set was a tough one to swallow. I'm very happy I managed to turn it around."
Sinner's right foot was bloodied, turning his sock and shoe red, but the 24-year-old said: "I'm good, it seems much worse than it is, just a nail."
Novak Djokovic, still seeking that record-breaking 25th grand slam win, did not find it easy either. China's Wu Yibling, 99th in the world and a first-round loser at his only previous Wimbledon in 2023, proved a resilient opponent.
With night drawing in the roof needed closing, then the curfew beckoned before the Serb wrapped it up just in time 6-4 5-7 6-4 6-4.
"It was really challenging for me," said Djokovic.
"He put me under pressure and surprised me with the level of every shot. At one point he didn't really have a weakness - I probably should have lost the fourth set.
"On this surface the match can be decided in a few shots and thankfully I have experience over the last 20 years of this court that can help me manage the situation. But it would be nice to have that experience and a new fresh body."
Third seed Felix Auger-Aliassime brushed past Aleksandr Shevchenko 6-3 6-1 6-4, while Daniil Medvedev beat Marin Cilic, the 2017 finalist but now 37, 6-1 6-2 6-4.
But some big guns exited. Casper Ruud, Andrey Rublev and Luciano Darderi, seeded 11th, 12th and 14th respectively.
Norwegian Ruud's exit was no great shock. His conqueror, Hubert Hurkacz, who won 6-4 6-2 7-6 (9-7) is a threat on grass, while Rudd has never gone beyond the second round at Wimbledon.
Rublev lost a near four-hour scrap to 132-ranked fellow Russian Roman Safiullin 6-4 6-7 (8-6) 3-6 6-3 7-6 (14-12), while Italian Darderi lost in straight sets to American Ethan Quinn.
A trio of rising stars all progressed without alarm.
American 16th seed Learner Tien, 20, beat Czech Dalibor Svrcina 6-1 6-4 6-7 (4-7) 6-3. Spaniard Rafa Jodar, 19 and â� on his Wimbledon debut, dispatched British wildcard Felix Gill 6-3 6-3 7-5. Joao Fonseca, also 19, saw off Spanish veteran Roberto Bautista Agut 7-6 (7-4) 6-4 6-3 in time to watch Brazil at the World Cup.
14°C