The "Before Sunset" actor beat the likes of Adam Driver, Ben Foster, Richard E. Grant and Lakeith Stanfield to take home the Best Actor prize for his role as a troubled priest in "First Reformed", which also won Best Screenplay for director Paul Schrader.
In his acceptance speech, Hawke made a political statement, telling the audience at New York's Cipriani Wall Street, "We are living in a time when there's a void of political and spiritual leadership. In that kind of time period, a heavy burden falls upon the arts. ... We must not give in to tribal thinking, we are the great generators of empathy and compassion".
Collette was a surprise Best Actress winner, beating the likes of Kathryn Hahn, Regina Hall, Michelle Pfeiffer and major Oscar contender Glenn Close to secure the prize for her role in indie horror "Hereditary".
The only other project to win multiple accolades was "Eighth Grade", as Bo Burnham took home the Bingham Ray Breakthrough Director Award and newcomer Elsie Fisher was given the Breakthrough Actor award.
The Best Feature category went to "The Rider", while the Audience Award was bestowed upon "Won't You Be My Neighbor?", a documentary about beloved children's TV host Fred Rogers. "Hale County This Morning, This Evening" was named Best Documentary and TV shows "Killing Eve" and "195 Lewis" won the Breakthrough Series prizes.
Weisz was also honoured with a career tribute alongside Willem Dafoe and director Paul Greengrass.
According to Deadline, Dafoe got choked up when he paid tribute to Italian director Bernardo Bertolucci, who had passed away earlier that day.
"I knew him a little bit. He was not only influential for other filmmakers but he was very generous to other filmmakers. It's important to remember when people pass," he said.
The list of winners is as follows: