In 2010, McCarthy was cast in a leading role on the CBS sitcom Mike & Molly. Television critic Lucy Mangan from the Guardian commended McCarthy and her co-star Billy Gardell on some “unfeasibly delicate and charming work”, while decrying the show itself for hanging every one of its gags on the subject of their weight. In 2011, McCarthy had a breakout performance in the comedy film Bridesmaids alongside Kristen Wiig, Maya Rudolph, Rose Byrne, Wendi McLendon-Covey and Ellie Kemper. She received wide critical acclaim and press coverage for her performance. McCarthy received an Academy Award nomination for Best Supporting Actress for her performance. She received BAFTA, Critics' Choice and Screen Actors Guild Awards nominations, as well as won Boston Society of Film Critics Award, New York Film Critics Online Award for Best Supporting Actress, Women Film Critics Circle Award for Best Comedic Actress, and MTV Movie Award for Best Comedic Performance.
One of McCarthy's most memorable scenes in Bridesmaids was improvised, according to director Paul Feig. In fall 2011, after achieving fame from Bridesmaids, she received her first Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series for her role on Mike & Molly.
In June 2011, she hosted the Women in Film Crystal + Lucy Awards. She was invited to join the Academy of Motion Picture Arts and Sciences in June 2012 along with 175 others. McCarthy hosted Saturday Night Live on October 1, 2011, April 6, 2013, February 1, 2014, February 13, 2016, May 12, 2017 and December 6, 2025. She was nominated five times for a Primetime Emmy Award for Outstanding Guest Actress in a Comedy Series for her appearances on the television show from 2011 to 2017, winning in 2017. In 2011, McCarthy produced a CBS pilot which starred her husband, Ben Falcone. After her Bridesmaids breakout, McCarthy had supporting roles in the comedy films This Is 40 (2012), the spinoff to Judd Apatow's film Knocked Up, and The Hangover Part III (2013).
In 2013, McCarthy co-starred in the crime comedy Identity Thief with Jason Bateman. Identity Thief, her star vehicle, opened at No. 1 at the box office, and grossed $174 million worldwide despite negative reviews. R. Kurt Osenlund of Slant Magazine praised McCarthy's performance, writing that she "gives a performance leagues better than anything to be expected in a mainstream, early-in-the-year release, padding a typically sketched character with layers of hilarity and pathos. McCarthy owns 'Identity Thief' with a turn of limitless surprise, making an otherwise adequate comedy soar as a star vehicle. She is riveting in simply-penned moments of remorse and confession, adding tearful depth to her ace timing and formidable physical comedy." Peter Debruge of Variety magazine praised McCarthy but criticized the script, saying "Melissa McCarthy proves she’s got what it takes to carry a feature, however meager the underlying material." She received People's Choice and MTV Movie Awards nomination for her performance. Later in 2013, McCarthy co-starred with Sandra Bullock in the buddy cop comedy The Heat. The film was released in the United States and Canada on June 28, 2013, to both critical and commercial success. With McCarthy being called "box office gold," The Heat grossed $229 million worldwide. She won American Comedy Award for Best Comedy Actress - Film, and well as received nominations an Critics' Choice Movie Award for Best Actress in a Comedy and MTV Movie Award for Best Comedic Performance.
In 2013, McCarthy founded the production company On the Day Productions with her husband Ben Falcone. Tammy was the company's first project. The film cost $20 million. McCarthy co-wrote the script for the road comedy film, which was released in 2014. McCarthy's character loses her job and her car, and then learns that her husband has been unfaithful. To get away, she is forced to rely on her alcoholic grandmother (Susan Sarandon) for transportation as they embark on a journey of self-discovery. Although a box office success, grossing over $100 million from a $20 million budget, it received highly negative reviews from critics with McCarthy received Razzie nomination for Worst Actress. On Rotten Tomatoes, the site's critical consensus reads, "Melissa McCarthy remains an engaging screen presence, but her efforts aren't enough to keep the jumbled Tammy on track." Later in 2014, McCarthy played the female lead, opposite Bill Murray, in the comedy-drama film St. Vincent, directed and written by Theodore Melfi. The film received positive reviews from critics and her performance as an overworked single mom was noted. At the 20th Critics' Choice Awards, she received Best Actress in a Comedy Movie nomination.
In May 2015, McCarthy received a star on the Hollywood Walk of Fame. In August 2015, Forbes ranked her as the third highest-paid actress of 2015, with earnings of $23 million. Also in 2015, McCarthy played the lead in frequent collaborator Paul Feig's spy comedy Spy, a role that earned McCarthy her first Golden Globe Award nomination for Best Actress in a Motion Picture – Musical or Comedy. The film received positive reviews from critics and grossed $235 million worldwide against a $65 million budget. McCarthy's performance was praised by critics. Richard Roeper of The Chicago Sun Times called her "as funny and as winning as anyone in the movies these days". Tom Russo of The Boston Globe credited the film's success to McCarthy, writing, "part of what makes the action comedy such a loopy blast is the identity shifts she pulls on the audience." Bill Goodykoontz of Arizona Republic called the film McCarthy's return to form, writing "Finally, after the promise shown in Bridesmaids, but sold short since by weak scripts in films like Tammy and Identity Thief, Melissa McCarthy gets a movie vehicle worthy of her talents."
In 2016, McCarthy starred in the comedy film The Boss, a film based on a character which McCarthy had created in the Los Angeles Groundlings – a wealthy businesswoman "who goes to jail for insider trading, and struggles to reinvent herself as America's new sweetheart when she's released". Although it received generally negative reviews from critics, it grossed over $78 million worldwide on a budget of $29 million. Also that year, she played an author and scientist in the all-female reboot of Ghostbusters, directed by Paul Feig. The film grossed $229.1 million worldwide against its $144 million budget, making it a box office bomb with losses of over $70 million following theaters taking their revenue cut. At the 43rd People's Choice Awards, McCarthy won Award for Favorite Comedic Movie Actress.
In 2016, she recorded the song "Anything You Can Do (I Can Do Better)" with Barbra Streisand which appears on Streisand's album Encore: Movie Partners Sing Broadway. On February 4 and 11, 2017 she made surprise appearances on Saturday Night Live portraying White House Press Secretary Sean Spicer. She returned to the show to portray Spicer on April 16 and May 13, 2017 (also hosting the latter). McCarthy also appeared in a Super Bowl LI ad for Kia Motors, promoting the Kia Niro. McCarthy played a wannabe environmentalist, who has a series of mishaps befall her such as being capsized by a whale, being charged by a rhino, and falling down a crevasse. The commercial featured the song "Holding Out for a Hero".
