Rodriguez made her screen debut appearing in an episode of Law & Order in 2004. She later has appeared on Eleventh Hour, Army Wives and The Mentalist. On October 19, 2011, Rodriguez landed the recurring role, Beverly, in the soap opera series The Bold and the Beautiful. She received a role in the musical film Go for It!, for which she received a 2011 Imagen Awards nomination.

At the age of 16, she was among thirteen teenagers to be accepted into Columbia University’s Theatrical Collaboration. She attended NYU’s Tisch School of the Arts. She trained for four years at the Atlantic Theater Company and Experimental Theatre Wing, and earned with a Bachelor of Fine Arts degree in 2005.

In 2012, Rodriguez played young hip-hop artist Majo Tenorio in the independent musical-drama film Filly Brown, for which she won an Imaged Award. She received good reviews for her performance in film. She also was the recipient of the Best Actor Award at the First Run Film Festival in New York. On June 9, 2013, Gina won the Inaugural Lupe Award. On April 16, 2013, during an interview, she revealed she was offered a role in the Lifetime television series Devious Maids, but turned it down. On October 16, 2013, she joined the cast of the movie Sleeping With The Fishes. She is also working on an album.

On February 27, 2014, Entertainment Weekly announced that Rodriguez would play the titular role of Jane Villanueva in Jane the Virgin, for which she went on to win a Golden Globe Award. On June 4, 2014, Rodriguez joined the cast of the upcoming drama film Sticky Notes. In August 2015, she co-hosted the 2015 Teen Choice Awards with Ludacris and Josh Peck. She voiced Mary in the animated film The Star, which was released in November 2017, and played Anya in the science fiction thriller film Annihilation, opposite Natalie Portman. She also voices Carmen Sandiego in the Netflix animated series Carmen Sandiego which premiered on January 18, 2019. In March 2018, Netflix announced that they had acquired the live-action film rights for Carmen Sandiego and that Rodriguez would star as Sandiego in the film.

In an interview, Rodriguez revealed that she has suffered from Hashimoto’s disease, a thyroid condition, since the age of 19. In a 2014 interview, she said, “I grew up Catholic. I have Jewish in my family and I attend a Christian church in Hollywood. I am basically all over the place.”

Rodriguez has been increasingly involved with various charities and philanthropic efforts, made possible by her rising visibility as a film and television actress. Most notably, she became involved with various organisations in 2015, ranging from CustomInk to Naja Lingerie, all of which Rodriguez has stated have a special connection to her life and experiences.

On March 16, 2015, she was announced as a new member of the HSF’s (Hispanic Scholarship Fund) Board of Directors. The HSF is the United States’ biggest non-profit organization which supports Hispanic American higher education. Because attaining an education was the biggest priority in Rodriguez’s household, coupled with her determination to work towards a degree, she was able to work towards receiving a HSF scholarship. For her placement on the Board of Directors, Rodriguez will help to support HSF in a matchless and meaningful way, therefore making sure that HSF’s mission will continue to support the original values and commitment to education. Rodriguez has stated that this is a great opportunity to say thank you [to the HSF] and to help open doors for Latino students to follow.

Later in 2015, PACER’s (The Parent Advocacy Coalition for Educational Rights) National Bullying Prevention Center teamed up with CustomInk and enlisted the help of various celebrities, Rodriguez among them, to raise money for their fifth annual “Be Good to Each Other Campaign”. Throughout the month of October 2015, people were encouraged to purchase a celebri-tee from CustomInk, who would donate all the proceeds from bullying prevention T-shirts to PACER. Rodriguez, in designing a celebri-tee which featured the phrase “Kindness Is Always In Style” in cursive print, took a stand for kindness, acceptance, and inclusion in support of bullying prevention, and stated that her parents always taught [her] the power of thinking positively and treating others with respect. She also hopes that through the Be Good to Each Other Campaign, such a message could be continued to be spread to younger generations.

Also in October 2015, Rodriguez was announced as a partner of Naja, a lingerie line founded in 2014 with ambitions to help women and the environment. Because Naja is vertically-integrated, thereby shortening manufacturing lead times by up to eighty percent, it allows the company’s savings to go towards school books, lunches, and uniforms for employees’ children, and there’s also an emphasis on a flexible work environment. Having seen the hardships of single mothers through a close friend from college, Rodriguez wanted to support a company that primarily employed single mothers and allowed them to work from home and provide for their families. She also cites Naja’s commitment to creating lingerie for women of all shapes and sizes and encouraging body confidence as a factor for becoming involved with the lingerie line; admitting that it was a process for her to fall in love with her own body, Rodriguez also spoke on the importance of empowering women to love their own bodies and what they wear. Naja is also environmentally-conscious in its production, as more than half of all of its pieces are made of synthetics (like nylon)—that have been fabricated from recycled plastic bottles—and makes use of digital printing as a more environmentally-friendly measure.

In 2016, Rodriguez began dating actor, model, and MMA fighter Joe LoCicero, whom she met on the set of Jane the Virgin. On August 7, 2018, Rodriguez confirmed in an interview with Us Weekly that she and LoCicero were engaged. On May 4, 2019, the couple married.

In 2016, Rodriguez was named to Oprah’s SuperSoul 100 list of visionaries and influential leaders. In 2017, Rodriguez, among several other artists, sang on the single “Almost Like Praying”. Sparked by Lin-Manuel Miranda, creator of Broadway’s Hamilton, all proceeds from the song benefited those affected by Hurricane Maria in Puerto Rico.

Rodriguez owns the production company I Can & I Will Productions. She developed projects at CBS and The CW that are centered around the Latino community. In 2018, it was announced that she would produce and star in Netflix romantic comedy film Someone Great.

In 2019, Rodriguez starred as the titular character in the action thriller film Miss Bala. In the same year, it was announced that Rodriguez was cast in the upcoming Netflix science fiction thriller Awake. She also voiced the role of Velma Dinkley in the computer animated adventure film Scoob!.

In October 2019, Rodriguez came under fire for her use of the “n-word” during an Instagram livestream, where she sang the song “Ready or Not” by the Fugees, including the line in which the singer Lauryn Hill uses the slur, to which Rodriguez raps along to. She faced widespread social media backlash for this, and soon posted an apology which was largely rejected for being insincere and dismissive. She posted a second, more heartfelt, apology later.