Ruffalo earned a record-tying four nominations for the Academy Award for Best Supporting Actor for playing a sperm donor in the comedy-drama The Kids Are All Right (2010), Dave Schultz in the biopic Foxcatcher (2014), Michael Rezendes in the drama Spotlight (2015), and a debauched lawyer in the comic fantasy Poor Things (2023).

[9] "I grew up in a household that had three religions in it, (born-again) Christianity, Catholicism and Bahai'ism, so there were different viewpoints and a lot of debate about that, and I immediately began to understand that all these people that I loved very much had very strong feelings about faith, but all of them were valid to me.

He moved with his family to San Diego, California, and later to Los Angeles, where he took classes at the Stella Adler Conservatory and co-founded the Orpheus Theatre Company.

[17] Ruffalo had minor roles in films including The Dentist (1996), the low-key crime comedy Safe Men (1998), and Ang Lee's Civil War western Ride with the Devil (1999).

It led to other supporting roles, including the films XX/XY (2002), Isabel Coixet's My Life Without Me, John Woo's Windtalkers (2003), Jane Campion's In the Cut (2003) and We Don't Live Here Anymore (2004).

That same year he also acted in Michel Gondry's romantic fantasy drama Eternal Sunshine of the Spotless Mind (2004) starring Kate Winslet and Jim Carrey.

[3] In 2006 he starred in the political drama remake All the King's Men acting opposite Sean Penn, Kate Winslet, Jude Law, and Anthony Hopkins.

Charles Isherwood of The New York Times wrote of his performance, "Nobody slings it with more panache than Mark Ruffalo, the soulful movie and stage actor making his Broadway debut here.

"[19] David Rooney of Variety wrote "The most arresting work onstage comes from Ruffalo, channeling prickly charm into a proud man who uses glib aggression to camouflage his frustration.

[21] That same year, Ruffalo played divorced lawyer Dwight Arno, who accidentally kills a child and speeds away, in Terry George's film Reservation Road, based on the novel by John Burnham Schwartz.

[30] Peter Bradshaw of The Guardian praised Ruffalo's work writing, "Ruffalo actually makes Bruce and Hulk interesting, even droll characters (he also plays the monster in mo-cap), superior to the Eric Bana and Edward Norton incarnations, and his version ingeniously locates the big green monster's secret not in the over-rehearsed subject of "anger management" but depression and self-hate.

The following year, Ruffalo starred as Ned Weeks in the HBO television adaptation of Larry Kramer's AIDS-era play, The Normal Heart (2014), his performance earned him an Emmy nomination.

"[35]Also in 2014, Ruffalo received his second Academy Award nomination for his portrayal of wrestler Dave Schultz in the biographical drama Foxcatcher directed by Bennett Miller.

Ruffalo told The Hollywood Reporter that he met with Rezendes and studied him as research for the film saying, "I spent a lot of time with the real journalist, I had meals with him.

[46] In 2022 he acted in the Netflix science fiction action comedy The Adam Project opposite Ryan Reynolds, Jennifer Garner, and Zoe Saldana.

[54] On December 1, 2008, Ruffalo's younger brother, Scott, was found outside his home on North Palm Drive in Beverly Hills with an execution-style bullet wound to the head.

[61] The lawsuit claims that the residents suffered physical and emotional injuries and added that the fire caused damage to their homes and exposed them to toxic fumes.

"[66][67] Ruffalo signed a letter supporting Labour Party leader Jeremy Corbyn, which described him as "a beacon of hope in the struggle against emergent far-right nationalism, xenophobia and racism in much of the democratic world" and endorsed him for in the 2019 UK general election.

[76] He claimed in the December 2010 issue of GQ that after he organized screenings in Pennsylvania of a documentary about natural-gas drilling called Gasland, he was placed on a terror advisory list.

[80] In 2019, Ruffalo starred in and co-produced Dark Waters, which spotlighted another one of his environmental concerns with its true-life depiction of a corporate lawyer's relentless pursuit of justice to expose poisonous pollution by chemical behemoth DuPont.

[82] In October 2019, Ruffalo tweeted that "until George W. Bush is brought to justice for the crimes of the Iraq War, (including American-led torture, Iraqi deaths & displacement, and the deep scars—emotional & otherwise—inflicted on our military that served his folly), we can't even begin to talk about kindness.

"[83] In October 2020, speaking to Mehdi Hasan, Ruffalo condemned what he called Israel's "asymmetrical warfare" against the Palestinians, stating, "There is no reason that an ally of America should not be held to the same standards as any other nation in the world."

[87] In November 2023, Ruffalo criticized the prime minister of Israel, Benjamin Netanyahu, for describing the civilian deaths during the Israeli attacks on Gaza as "collateral damage".

[89] In September 2024, Mark Ruffalo, alongside Susan Sarandon, Cynthia Nixon, and Rosie O'Donnell, signed an open letter from SAG-AFTRA and Sister Guild Members calling for a ceasefire and condemning the “industry's McCarthyist repression of members who acknowledge Palestinian suffering.” This letter followed the firing of Melissa Barrera from the Scream franchise in November, due to her comments on the Israel–Hamas War, in which she expressed support for Palestine.

He has explained his opinion by saying: "I don't want to turn back the hands of time to when women shuttled across state lines in the thick of night to resolve an unwanted pregnancy, in a cheap hotel room.

[94] In 2015, Ruffalo supported the "Education Is Not a Crime" campaign alongside other artists and intellectuals, including Nazanin Boniadi, Abbas Milani, Mohsen Makhmalbaf, Azar Nafisi, Omid Djalili, Eva LaRue, Mohammad Maleki (former president of the University of Tehran), and Nobel Peace laureates such as Archbishop Desmond Tutu, Shirin Ebadi, Tawakkol Karman, Jody Williams, and Mairead Maguire, to draw attention to the Iranian government's systematic denial of university education to young Baha'is.

[95] In 2023, Ruffalo sought to block the sale of the West Park Presbyterian Church, a city landmark built in the 1880s, to prevent its demolition and construction of housing in its place.

"[97] February 2016, Ruffalo tweeted a Tech Times article in which a group of Argentinian doctors attributed the cause of a microcephaly outbreak in Brazil to the use of a larvicide chemical added to reservoirs of drinking water to combat dengue fever, rather than the Zika virus.

[98] The New York Times described the claim as "dubious" and stated that those "sounding the alarm", did not mention that the larvicide did not work through the central nervous system and that it has been approved by the World Health Organization.

His EGOT recognitions are: On February 8, 2024, accompanied by his wife Sunrise Coigney as well as the two elder of his three children, Ruffalo received a star on the Hollywood Walk of Fame.