Stars arriving under bright California skies in couture gowns and extravagant jewels were greeted by the British comic's signature cutting one-liners at the awards ceremony, the first of the year building up to next month's Oscars.
"Let's go out with a bang, let's have a laugh at your expense, shall we?" joked Gervais, hosting the awards for the fifth and final time, before tearing into the industry.
Mendes defeated Hollywood heavyweights Martin Scorsese and Quentin Tarantino, as well as South Korean auteur filmmaker Bong Joon-ho, in the crowded best director category.
"Goodness me, that is a big surprise," said a stunned Mendes.
"Can I just say there's not one director in this room, not one director in the world that is not in the shadow of Martin Scorsese? I just have to say that," he added to loud applause.
South Korean black comedy "Parasite" bagged the award for best foreign language film, as was widely expected, while Tom Hanks welled up thanking his family as he accepted a lifetime achievement award.
- 'Succession', 'Fleabag' win TV honors -
In his opening speech, Gervais tackled topics haunting the entertainment sector including #MeToo, lack of diversity, and the streaming wars, to name but a few.
An off-color joke about British actress Judi Dench and the critically slammed film "Cats" was bleeped out by censors.
Beyonce and husband Jay-Z were in attendance to watch a starry list of award presenters including Pitt, his co-star Leonardo DiCaprio and Jennifer Lopez ("Hustlers").
Among the Globes handed out on the TV side, HBO hit "Succession" won best drama, fending off Netflix's flagship "The Crown." Its star Brian Cox won for best actor.
But "Crown" star Olivia Colman scooped best actress for her turn as Queen Elizabeth II.
Phoebe Waller-Bridge added a best comedy actress Globe to her Emmy win for her show "Fleabag," which also won overall top comedy honors.
- Netflix's night? -
Netflix -- which has disrupted the film industry in recent years -- began the night far ahead of the traditional Hollywood studios with 17 Globe movie nominations.
It has multiple frontrunners to scoop the night's most prestigious film prize, best drama -- including Martin Scorsese's gangster epic "The Irishman," "Marriage Story" and "The Two Popes."
Warner Bros. dark comic tale "Joker" and "1917" round out the category.
Streaming giant Netflix only began producing original movies in 2015, but has spent billions to lure the industry's top filmmaking talent -- and to fund lavish awards season campaigns.
"This show should just be me coming out, (saying) 'You win everything, Netflix, good night," joked Gervais.
The streamer picked up an early win with Laura Dern's supporting turn in "Marriage Story," a heart-wrenching divorce saga starring Scarlett Johansson and Adam Driver.
Netflix also has Eddie Murphy's comeback vehicle "Dolemite Is My Name" in the best comedy or musical race -- unlike the Oscars, Globes organizers split films into two categories.
In the drama acting categories, Joaquin Phoenix is favorite in a crowded field for his radical portrayal of the villainous anti-hero in "Joker."
But Driver's intense turn in "Marriage Story" has generated significant buzz, while the ever-popular Antonio Banderas has been hailed for a career-best performance in Pedro Almodovar's "Pain and Glory."
Renee Zellweger looks in a formidable position to pick up the best actress gong with Judy Garland biopic "Judy."
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