A unique set of challenges makes the smoky track in the heat and humidity of Singapore's tropical climate the hardest physical test of the season.
The duration of the race, with each of the 61 laps of the 5,063-kilometer track with 23 turns and 80 gear changes, more than any other in the Formula One calendar, means that drivers and machinery are working up to the limit.
"I spent it, it felt like the longest race of my life, so I'm glad it's over," said Hamilton when he was interviewed on the track after hugging his crew to celebrate. "Max made a great fight too, but what a day, what a weekend."
Hamilton had the perfect start from pole position, since Verstappen was slower from second on the dirty side of the grid and saw that his Red Bull was immediately pressed by Vettel.
The four-time German world champion used his superior Ferrari power to overtake Verstappen on Raffles Boulevard and managed to overtake the Dutchman before the safety car temporarily stopped hostilities in the first round for the third consecutive year in Singapore.
It was triggered by a collision between Force Indias that put Esteban Ocon on the wall and out of the race after a side blow from teammate Sergio Pérez.
Hamilton controlled the restart four laps later to run more than a second of Vettel.
The championship leader had extended his lead to around three seconds when, on lap 14, Vettel was the first to nail ultra-smooth tires, but it soon seemed an unwise move as he joined behind the slower Perez Force India.
Hamilton responded immediately and pitted on the next lap, but opted for the soft compound that had been predicted to last until the end.
Vettel's frustration grew when Hamilton joined the front and then overflowed when Verstappen jumped on him when he also faced the soft.
There are no "chances" to win, Vettel moaned on the team's radio.
"We're too late again," he shouted. "These tires will not reach the end."
When the last of the favorites, Daniel Ricciardo, faced the ultra-shorts on lap 27, he left the first six on the grid: first Hamilton, Verstappen second and Vettel third.
Hamilton kept control, but he got nervous in front. "I feel like we've stopped too early," he said, as some patches of rain began to circle the circuit.
"No, we look good compared to those around us," said race engineer Peter Bonnington.
Hamilton endured a challenge from Verstappen as the pair made its way through some back markers.
But after that, Hamilton achieved victory, despite reporting that he had to work hard "to maintain the temperature on these tires."
Valtteri Bottas guided his Mercedes to fourth place, Kimi Raikkonen's Ferrari came in fifth and Daniel Ricciardo was sixth in the second Red Bull.