The outspoken and prolific 76-year-old actor was presented with the prestigious honor by Leonardo DiCaprio, who has also been front and center during this year's awards season. He told the crowd it was an "absolute honor" to present De Niro, whom he'd watched and studied as a young man, with the award.
De Niro received a standing ovation as he took to the stage.
"As actors, we don't take victory laps. We're too worried about what our next job is going to be," he began his acceptance speech, teasing a project he's about to film with co-star DiCaprio and director Martin Scorsese. "At least I know I've got another year of health insurance."
"I've been puzzled over what to say to express my appreciation for this award tonight," he continued, "but more than that, being a part of this community of actors, for being able to have a career with dignity, and creative fulfillment."
"We, as actors, don't do it all alone. We can't do it all alone. We depend on each other for collaboration in our work and support and fellowship both onscreen and off, and for that, I am so grateful."
He went on to thank SAG-AFTRA, before pointing out we are living in a time where there is hostility toward unions. He also brought attention to a "dire" political situation, which he said is "so deeply concerning to me."
"There is right and there is wrong, and there is common sense and there is abuse of power. And as a citizen, I have as much a right as anybody -- an actor, an athlete, a musician, anybody else -- to voice my opinion. And if I have a bigger voice because of my situation, I am going to use it whenever I see a blatant abuse of power," he said as the crowd applauded.
The hard-earned recognition from the Screen Actors Guild comes less than a week after the announcement of this year's Oscar nominees, where De Niro was surprisingly snubbed in the Best Actor category.
However, De Niro appeared in two of the most nominated films of the year. The two-time Oscar winner stars in Martin Scorsese's The Irishman -- which managed to snag an impressive 10 nominations -- and plays a key role in Joker, which was nominated for a record-setting 11 nominations.
De Niro is nominated, along with his fellow Irishman co-stars, at this year's SAG Awards, where the star-studded ensemble is up for Outstanding Performance by a Cast in a Motion Picture.