The director and his stars, including Margot Robbie, Leonardo DiCaprio and Brad Pitt, were in Cannes for the film's world premiere, and Quentin was clearly moved by the reaction of the audience as the end credits rolled.
"Thank you for being such a fantastic audience for the first time we've ever showed it to an audience," he told the crowd after the screening.
The film's premiere took place exactly 25 years after Tarantino's "Pulp Fiction" screening at the festival. That movie went on to win the coveted Palme d'Or. His last project to screen at Cannes was "Inglourious Basterds" a decade ago (2009).
Hours before the premiere, Sony bosses released the full trailer for the period movie, which is set in the late 1960s. "Once Upon a Time in Hollywood" hits cinemas in the U.S. on 26 July.
Ahead of his latest Cannes launch, Tarantino asked fans not to spoil the film's plot twists for others and before the screening, Cannes boss Thierry Fremaux reminded the audience to remain tight-lipped about the movie.
"It's a bit exceptional because the production and Quentin Tarantino asked me to ask you not to discuss the film," he said. "They would greatly appreciate that you not reveal anything that would prevent audiences worldwide from experiencing what you do today."
Meanwhile, there was chaos on the red carpet just before the screening when hundreds of ticket holders were turned away from the premiere at the Grand Lumiere.
More than 100 balcony ticket holders were held at the edge of the red carpet for an hour as those with seats in the orchestra and mezzanine were fast-tracked into the venue - before the balcony guests were then informed there was no space for them.
To make matters worse, security staff insisted those contesting the decision not to let them in risked arrest if they did not leave the red carpet.
Some of the film fans left out in the cold had paid $1,000 (£790) for their tickets.