He has won several accolades, including a Volpi Cup for Best Actor, and has been nominated for the Palme d'Or, the Golden Lion, and the Bronze Horse.

Gallo later became an actor and starred in films including Arizona Dream (1993), The House of the Spirits (1993), Palookaville (1995), The Funeral (1996), Freeway II: Confessions of a Trickbaby (1999), Trouble Every Day (2001), Stranded (2001), Tetro (2009), Metropia (2009), Essential Killing (2010), and The Legend of Kaspar Hauser (2012).

As a filmmaker, Gallo directed, wrote, and starred in three independent films, Buffalo '66 (1998), The Brown Bunny (2003), and Promises Written in Water (2010).

Gallo has also directed and starred in numerous short films, including The Agent (2010), and several music videos, such as Going Inside, Cosmopolitan Bloodloss, and 99 Problems.

As a model, he has been photographed for several fashion houses and brands including Calvin Klein, H&M, Supreme, Persol, and Yves Saint Laurent.

Fans of Gallo's work have notably included Jean-Luc Godard, John Waters, Werner Herzog, Claire Denis, David Lowery, and Robert Pattinson.

In 1984, Gallo acted in the No Wave film The Way It Is or Eurydice in the Avenues (1985) by Eric Mitchell, along with actors Steve Buscemi, Edwige Belmore, Mark Boone Junior and Rockets Redglare.

[21] In 2003, Gallo starred in and directed the film The Brown Bunny, which chronicles a motorcycle racer's cross-country road trip and co-starred Chloë Sevigny.

[22] Ebert then responded – adapting a statement made by Winston Churchill – that, "although I am fat, one day I will be thin, but Mr. Gallo will still have been the director of The Brown Bunny.

"[20] Gallo was strongly considered for and almost cast as Uncle Rico in the 2004 film Napoleon Dynamite, though the role ultimately went to Jon Gries.

[27] In 2010, Gallo won the Volpi Cup for Best Actor at the 67th Venice International Film Festival for his non-speaking role in Essential Killing.

Gallo did not attend the ceremony to accept his award in person, leaving the duty to the film's director Jerzy Skolimowski, who tried to get the actor to reveal himself, leading the audience in a chant of his name.

It states that the film is 88 minutes long, stars Gallo as the lead character Seth Goldstone, and co-stars pornographic actor Jamie Gillis.

[41] In 1984, Gallo (using the name "Prince Vince") also appeared as a dancer on an unsold TV pilot for a hip-hop dance show called Graffiti Rock.

He played in a rock band with Lukas Haas called Bunny, and Gallo put out his own album which he wrote, performed and produced under Warp Records, titled When.

[53] Gallo previously owned a condo at Trump Tower, as well as apartments in buildings designed by Jean Nouvel and Richard Meier.

[5] In 2004, Gallo appeared in the documentary, Rated R: Republicans in Hollywood, discussing the political discrimination he has faced in the film industry as a conservative.

"[20][72] In 2022, he also praised then-Democratic Senator Kyrsten Sinema as an "open minded and thoughtful" politician, who "adds productive ideological diversity and balance to our beautiful country";[52] and donated $250 to the campaign of Republican Representative Juan Ciscomani.

[77][failed verification][better source needed] In 2009, Gallo instead listed Francis Ford Coppola's The Rain People (1969) as his favorite film.

He has listed The Boy in the Plastic Bubble (1976), All Fall Down (1962),[81] Lilith (1964), Mickey One (1965), The Ravine (1969), The Only Game in Town (1970), The Panic in Needle Park (1971), The Gambler (1974), The Death of Richie (1977), The Beyond (1981), and Deuce Bigalow: Male Gigolo (1999) among his favorite films.

[85] Although a member,[86] Gallo has expressed disdain for the Screen Actors Guild, calling them "a self-serving union that has never had the best intentions of its membership in mind".

[90] Film critic Roger Ebert frequently praised Gallo's performances, including those in The Brown Bunny (2004),[91] Tetro (2009),[92] Essential Killing (2010),[93] and 2 Days in New York (2012).

[94] Gallo's performance in Shut In (2022) was singled out and praised by Cath Clarke of The Guardian and John Semley of The New Republic, who gave the film itself negative reviews.

Buffalo '66 (1998) received generally positive reviews from critics, and was praised by Ebert,[97] Elvis Mitchell,[98] and Andrew Johnston.

[91] Moria McDonald of The Seattle Times gave the film a negative review, calling it a "self-indulgent and seemingly endless road movie".

[101] Promises Written in Water (2010) received mostly negative reviews, including from Leslie Felperin of Variety,[102] Deborah Young of The Hollywood Reporter,[103] and Xan Brooks of The Guardian.

The Brown Bunny (2004) has been praised by individuals including Jean-Luc Godard, John Waters, Werner Herzog, Sean Penn,[111] Josh Safdie,[112][113] Claire Denis,[114] and David Lowery.

"[118] Filmmaker Jerzy Skolimowski praised Gallo's performances and described him as a method actor, but stated that he was difficult to direct and prone to anger.

One of the smartest people I’ve ever met and known – funniest too";[113] while filmmaker Caveh Zahedi has written that Gallo is "one of the most talented directors of his generation".

Gallo's popularity in Japan led to him appearing or being referenced in several Japanese video games, manga comics, and anime films.