Hamilton’s Mercedes teammate Valtteri Bottas finished second, with Thai-born Briton Alex Albon an excellent third for Red Bull.
Ferrari duo, Charles Leclerc and four-time world champion Sebastian Vettel, finished eighth and 10th as the celebrations for the Prancing Horse team fell flat on one of its home circuits.
After six laps behind the safety car, Bottas led the field away, but behind him the pack had bunched too closely and Antonio Giovinazzi crashed into the back of Williams driver Nicholas Latifi, with McLaren’s Carlos Sainz ploughing into Alfa Romeo’s Giovinazzi and sending him into the air temporarily.
Haas driver Kevin Magnussen was also involved as all four cars went into the barriers on the straight.
Sainz was seen clutching his hand but fortunately all four men were unhurt in a terrifying incident.
“It could have been much worse with the speeds we do on the main straight — at 280 kph — and it is not a nice feeling,” said Sainz, who took a fine second at Monza. “That crash was properly scary.”
Haas driver Romain Grosjean took a stronger view in a foul-mouthed rant over race radio.
“That was (expletive) stupid from whoever was at the front,” he shouted. “They want to kill us or what? This is the worst thing I’ve seen ever.”
A perplexed Bottas asked Mercedes what had happened after the restart.
“I think, Valtteri, it was people going before you’d gone — so they concertinaed into each other,” said strategist James Vowles.
With a red flag deployed for the second week in a row while the debris was cleared, Hamilton swept past Bottas from a grid restart and quickly built a commanding lead.
But there was to be another twist after Racing Point’s Lance Stroll crashed into the barriers, leading to a second red flag and another lengthy delay and restart.
Once again Hamilton was the fastest away, with Daniel Ricciardo, who eventually finished a fine fourth for Renault, briefly getting past Bottas before the Finn retrieved second place.
Hamilton drove untroubled to the finish for his 90th F1 victory, just one short of the all-time record held by Michael Schumacher.
In a poignant moment before the race start, Schumacher’s son Mick drove his 2004 Ferrari around the Mugello circuit in honor of Ferrari’s most successful driver.
Hamilton, who leads the title race by 55 points from Bottas, is set to claim his seventh world title to match another Schumacher record, but admitted the lengthy race had taken its toll.
“It was all a bit of daze. It was like three races in one day. Just incredibly tough today. This track is phenomenal and the heat and keeping Valtteri behind was not easy,” he said.
“My heart is racing. It is crazy to be here and to have 90 grand prixs.
“Justice for Breonna Taylor,” added Hamilton, who continues to highlight racial inequality with public displays at races, donning a t-shirt on the podium to that effect.
The F1 circuit next moves on to Sochi in Russia in a two weeks, a race won four times in the past by Hamilton, including last year.