[27][28] Hayek initially struggled with the lack of acting job offers after moving to the United States, recalling that "there was no industry or parts for Latin women",[26] and was once even told that her accent would "make moviegoers think of housekeepers".

[26] During this period, she secured guest-spots in television series such as Dream On (1992) and The Sinbad Show (1993) as well as supporting roles in the drama Mi Vida Loca (1993), and the made-for-Showtime thriller Roadracers (1994), her first collaboration with director Robert Rodriguez.

In 1994, Hayek was cast as Alma, a poverty-stricken young woman who becomes a sex worker, in Jorge Fons's drama El callejón de los milagros (Miracle Alley), which was based on the 1940s eponymous novel by Egyptian Naguib Mahfouz and translated from Cairo to Mexico City.

[29] In 1995, Robert Rodriguez and his co-producer and then-wife, Elizabeth Avellan,[25] cast Hayek opposite Antonio Banderas in the starring role of self-confident and feisty Carolina in Desperado, her breakout film.

[31] A brief role as a vampire queen followed in Rodriguez's cult horror film From Dusk till Dawn (1996), in which she performed an erotic table-top snake dance.

Critic Roger Ebert gave the film 3 out of 4 stars and described it as "a sweet, entertaining retread of an ancient formula", elevated by good performances (particularly Hayek's) and an insightful "level of observation and human comedy".

Ken Eisner of Variety wrote: "Russell Crowe and Salma Hayek make attractive leads, but they have neither the marquee power nor the requisite chemistry to keep Breaking Up from getting left at the altar of general distribution.

[36] In 1998, Hayek played an aspiring young singer in the 1970s New York City nightlife scene in Mark Christopher's drama 54, a doughnut shop waitress in Dan Ireland's dramedy The Velocity of Gary and a nurse in Rodriguez's supernatural horror film The Faculty.

In 1999, Hayek was unorthodoxly cast in Kevin Smith's religious satire Dogma as Serendipity, "the [Muse] who throughout history inspired all the geniuses of art and music, like Mozart and Michelangelo, and never got any of the credit".

[40] In 2000, Hayek had an uncredited role in Traffic, and played an aspiring actress in Mike Figgis' experimental film Timecode, a waitress in the Spanish drama Living It Up, and a cop and Playboy model in the heist comedy Chain of Fools.

In his review for the film, David Denby of The New Yorker concluded: "Smart, willful, and perverse, this Frida is nobody's servant, and the tiny Hayek plays her with head held high".

[49] In 2005, she served as a member of the 58th Cannes Film Festival jury, co-hosted the annual Nobel Peace Prize Concert with Julianne Moore in Oslo, Norway,[50][51] and directed a music video for Prince, titled "Te Amo Corazon" ("I love you, sweetheart") that featured Mía Maestro.

[52] Hayek appeared alongside her good friend Penélope Cruz in the 2006 Western comedy Bandidas, portraying two women who become a bank robbing duo in an effort to combat a ruthless enforcer terrorizing their town.

[60] In 2007, Hayek made a cameo appearance, as a nurse singing a cover of The Beatles song "Happiness Is A Warm Gun", in Julie Taymor's jukebox musical romantic drama Across the Universe.

The role of Madame Truska, a woman who can grow an indestructible beard, in Cirque du Freak: The Vampire's Assistant (2009), was Hayek's first acting project following the birth of her daughter.

[64] In 2010, Hayek played a fashion designer and the wife of a Hollywood talent agent (Adam Sandler) in the comedy Grown Ups which, despite a negative critical reception, made $271.4 million globally.

[66] A spin-off of the Shrek franchise, Puss in Boots received positive reviews from critics, grossed $554.9 million at the box office,[67] and was nominated for Best Animated Feature at the 84th Academy Awards.

In 2012, Hayek directed Jada Pinkett Smith in the music video "Nada Se Compara",[68][69] lent her voice for Peter Lord's animated film The Pirates!

In an Adventure with Scientists!, and played a cartel leader in Oliver Stone's action film Savages and a school nurse in Frank Coraci's comedy Here Comes the Boom.

Everly and Some Kind of Beautiful were both distributed for online markets and poorly received; while critics noted that the former "benefits from Joe Lynch's stylish direction and Salma Hayek's starring work, but it's too thinly written and sleazily violent to fully recommend",[73] Rotten Tomatoes gave the latter a 6% rating based on 34 reviews.

[75][76] In 2016, Hayek voiced the role of Teresa del Taco in Sausage Party, an adult animated film she described as "the naughtiest thing I've ever done.

[81] The comedy How to Be a Latin Lover (2017) was a sleeper hit upon its release and featured Hayek as the estranged sister of a man who has made a career of seducing rich older women.

[83] Hayek was cast as Eva Torres, a high-frequency trading executive, alongside Jesse Eisenberg and Alexander Skarsgård, in Kim Nguyen's tech drama The Hummingbird Project (2018), and as Nancy Teagarten, one half of a couple experiencing a series of financial crises, with Alec Baldwin, in Fred Wolf's comedy Drunk Parents (2019).

In 2020, Hayek appeared as a cosmetics mogul in Miguel Arteta's comedy Like a Boss, with Rose Byrne and Tiffany Haddish, and the alternative wife of a man in Sally Potter’s drama The Roads Not Taken, with Javier Bardem and Elle Fanning.

The drama Bliss (2021), which starred Hayek as a homeless woman befriending a recently divorced man (Owen Wilson), was released on Amazon Prime Video.

[86] Hayek portrayed Ajak, the wise and spiritual leader of the titular group, in the Marvel Cinematic Universe picture Eternals, directed by Chloé Zhao, who "personally selected" her for the role.

[93] Hayek then reprised her role as Kitty Softpaws in Puss in Boots: The Last Wish,[94] which received critical acclaim, grossed $485.3 million,[95][96] and like its predecessor was nominated for the Academy Award for Best Animated Feature.

[15] On December 13, 2017, Hayek published an op-ed in The New York Times stating that she had been harassed and abused by film producer Harvey Weinstein during the production of Frida.

[126] A July 2007 poll by E-Poll Market Research found Hayek to be the "sexiest celebrity" among a group of 3,000 public figures, with 65 percent of respondents using the term "sexy" to describe her.

[133] Throughout her career, Hayek has graced the covers of numerous international magazines,[134] including North America's InStyle, Elle, Premiere, Glamour and Variety;[134] Britain's Maxim, Marie Claire and Total Film;[134] and France's Entrevue and Madame Figaro.