Mendler has cited Bob Dylan as her biggest musical influence. To Ed Condran of Hartford Courant she said that: "You look at what Bob Dylan and artists like him have done and you just can't help but be blown away. I'm just glad I have the opportunity to start with this and I just want to take it as far as I can". In an interview with Disney Channel Netherlands, she revealed that her favorite song was "Don't Think Twice, It's All Right" from Dylan's 1963 album The Freewheelin' Bob Dylan. To Taylor Trudon of Huffington Post she said: "He was the first musician I got into where I paid attention to songwriting. He has a way of writing songs that's really playful with lyrics, but at the same time he's saying something that people feel is important and that they relate to. He spoke for a whole generation.". Also to Trudon, Mendler cited Etta James, Elvis Presley, B.B. King, Lily Allen, Ella Fitzgerald and Billie Holiday, and talked about these artists: "I love that they have soul in their voices. I think that's something important is having". Other musical influences include Elvis Costello, The Delfonics, Red Hot Chili Peppers and Van Morrison. During an interview with Yahoo!, in 2012, Mendler also commented that her first female influence was the R&B girl group Salt-N-Pepa and sang an impromptu a cappella rendition of the song "Shoop".

In 2004, Mendler got her first acting role in the animated Indian film The Legend of Buddha, in which she portrayed Lucy. When she was 13 years old, she got an acting role as a guest star on the soap opera General Hospital. She portrayed the dream child of character Lulu Spencer, in which the two have an argument on Mendler's character's birthday. The scene, lasting just under a minute, is later revealed to be a dream. That same year, Mendler was the voice of the character Thorn in the video game Bone: The Great Cow Race, which was based on the Bone comic series. In 2007, Mendler made her film debut in the film adaption of the Alice series, titled Alice Upside Down. Mendler starred alongside Disney Channel Actress Alyson Stoner and Lucas Grabeel. Mendler portrayed the antagonistic role of Pamela, who is the rival of Stoner's character, Alice. For the film's Soundtrack, Mendler provided backing vocals on the song "Free Spirit", performed by Stoner. Also in 2007 Mendler auditioned for Sonny with a Chance for the role of Sonny Munroe, but Demi Lovato was chosen. In 2008, it was announced that Mendler would play the role of Kristen Gregory in the film adaption of the popular teen novel series The Clique by Lisi Harrison. Mendler had the role of Kristen, a girl who attends OCD on a scholarship, and works hard to keep her good grades.

She also had begun working on a film with Actress and singer Lindsay Lohan titled Labor Pains, which kept being pushed back due to various conflicts and problems. Though initially slated for a theatrical release, the film did not receive one in the US and was instead released as a TV film on ABC Family in 2009. The film did, however, receive a theatrical release in countries such as Russia, Romania, Spain, the United Arab Emirates, Ecuador, and Mexico. The film drew 2.1 million viewers, a better-than-average prime-time audience for ABC Family, and per the network, was the week's top cable film among coveted female demographic groups. She had a supporting role in the film Alvin and the Chipmunks: The Squeakquel.

In 2010, Mendler became ambassador to First Book, a campaign to encourage reading and gives books to children in need. In 2011 it became part of Disney's Friends for Change, a pro-social "green" initiative of charity for environmental issues encouraging fans to take action. As campaign theme that year Mendler released a promotional single on June 11, "We Can Change the World", raising $250,000 for the Disney Worldwide Conservation Fund. She also participated of the Disney's Friends for Change Games, an Olympic-based televised games aired on the Disney Channel, getting $125,000 donation to UNICEF as Yellow Team captain and also competing for $100,000. But her team lost to the World Wide Fund for Nature. In 2012 Mendler won the honorary award Common Sense Media as Role Model of the Year for her work against bullying. Mendler was the third young Artist to win the award, which usually honors environmentalists and scholars. She also attended the annual UNICEF acoustic concert in New York to raise donations for charity in January 2013. In July 2012 Mendler became ambassador of the campaign Give With Target with Target Corporation to raise funds to reform schools in the United States. The campaign aims to get $1 billion by 2015. To start the Target campaign, they invested $5 million and distributed $25,000 grants to 100 in-need schools for the school year. Mendler said about the incentive: “I’m excited to partner with Target on their Give With Target campaign and celebrate the start of a new school year with kids across the country. It's so important for all kids to have everything they need for a successful school year”. In August she got $5 million donated by The Walt Disney Company and more $2 million donated by people at Facebook.

On March 31, 2011, it was confirmed that Mendler had signed with Hollywood Records, and had begun working on her debut album. Also in 2011 Mendler also starred the Disney Channel Original Movie Good Luck Charlie, It's Christmas!, which premiered on December 2, 2011. The song "I'm Gonna Run to You" was co-written and performed by Mendler, and was also featured in the film and released as promotional single on November 12, 2011. Mendler later co-wrote and sang the Disney's Friends for Change Games anthem called "We Can Change the World", released as her third promotional single on June 11, 2011. In 2012, she guest starred in the television series House as Callie Rogers, a homeless runaway teenager with a mysterious illness. She also made a guest cameo in Canadian teen drama Degrassi in the Season 11 episode "Don't Panic (1)" as Clare and Alli's friend Emily Quagmire, in their civics class; she can also be seen in the show's opening sequence sitting on Jake's red truck alongside Alli and Clare. She voiced the lead role of Arrietty in the American English dub of The Secret World of Arrietty, and she recorded a song "Summertime" for the movie which was released as a promotional single on February 2.

In 2012, Mendler signed with Target Corporation to release an exclusive line of clothing inspired by her character Teddy Duncan of Good Luck Charlie. The D-Signed by Teddy Duncan fashion collection includes clothing, accessories, hats, scarves, and souvenirs for girls in range from 4–18 years old.

In March 2013, a Spring edition was also released. While promoting her debut single "Ready or Not", Mendler signed with The Hunt, a mobile app which combines clothes and shows fashion tendencies. She released exclusively her music video and registered some personal clothes and fashion searches. She also had her own version in the games FanFUN FANfinity. While promoting her debut album Hello My Name Is..., Mendler offered exclusive album promotions through Target. In 2014 she signed with the line of dermatology products Clean & Clear and recorded several commercials and campaigns for real beauty.

On June 28, 2014, Mendler began the second leg of her Summer Tour, in Charlottetown, Prince Edward Island, Canada. On that date, she sang one of her new songs, "Fly to You", about a relationship that was said to be on the rocks but worth fighting for. On July 5, she performed another new song, "Deeper Shade Of Us", with disco influences. On November 25, 2014, Mendler was announced as a member of the main cast of the NBC comedy series Undateable in season two. She portrays the character Candace, an unlucky and undefeatably optimistic waitress, who becomes part of the main group. During the season, Candace and Justin, played by Brent Morin, were dating. After initial reports in July 2015, On July 2, it was confirmed that Mendler left Hollywood Records earlier this year. NBC renewed with Mendler for the third season that consisted entirely of live episodes, premiered in October 15.

In early 2015, NBC renewed with Mendler for a third season that consisted entirely of live episodes that premiered in October 15. In the season Justin proposes to Candace during a Backstreet Boys show and she accepts. On November 13, 2015, minutes before air time, a decision was made to pre-empt the then-upcoming live program due to the November 2015 Paris attacks. The next week, the live episode references were made about the attack as a tribute. Following the third season, it was announced that NBC had cancelled continuation of the series.

In 2016, Mendler produced her second studio album. Mendler discussed some of the producers and songwriters she was working with for the new album, including Mitch Allan, Dan Book, Alexei Misoul, Augie Ray, Beloryze, TMS, Ina Wroldsen, and Steve Mac. On August 4, 2016, Mendler announced the title of her new single, "Atlantis", featuring Kaiydo, which was released on August 26, 2016. The EP, Nemesis, was released on November 18. In October 2016 Mendler was cast as Ashley Willerman on the fifth season of the CMT television series Nashville. On February 3, 2017, Mendler announced her new single, "Temperamental Love" featuring Devontée. The music video was featured the Youtuber Jam in The Van. On February 10, Mendler was cast in lead role of the Fox comedy television pilot Thin Ice, created by Elizabeth Meriwether, but the network ultimately passed on the pilot in May. In May 2017 it was announced that Mendler will star in the Netflix comedy film Who Do You Think Would Win? along with David Spade, Joey Bragg, Matt Shively and Jackie Sandler. On August 25, 2017, Mendler released the third single from her upcoming album titled "Diving" with American group RKCB. The official music video was released hours after the release of the song.

She said hip hop band Fugees had great influence in her music training and also the recording of the debut album and song "Ready or Not", "One of the Writers was like ‘Check out this Fugees song, ‘Ready or Not’. So we all listened to it and were like that would be kind of fun to do some sort of interpolation off of that song, which is what we did. I think it stands by itself as its own song but it still has that memorable quality of the Fugees song, which is fun. I think we were all really proud of it and hoping it will go far". For her debut album, Hello My Name Is..., Mendler was inspired by indie pop Singers Ingrid Michaelson and Feist. She also mentioned Ed Sheeran and said she would love to write songs with him. Among the pop music artists, she cited Maroon 5, No Doubt, Destiny's Child, Justin Timberlake, Beyoncé and Bruno Mars. She cited Jamie Foxx as a great model of how to have a career in acting and music.

Thematically, Guilherme Tintel of Portal It Pop has noted that Mendler wasn't immature as the first work of other Hollywood artists. Tintel compares her songs to Jessie J, Katy Perry, Natalia Kills and Taylor Swift. Mendler said that the writing process isn't hard, because she was influenced by her own experiences. Her debut single, "Ready or Not", talks about self-confidence and deal with boys. To Pop Dirt Mendler said: "I consider myself to be that girl sitting at the curb waiting for the world, so I think it’s a great message to send to just go for the things that you want to take charge of". Her debut album discussed relationships ("Rocks at My Window", "Top of the World", "Love Will Tell Us Where to Go", "The Fall Song" and "Hold On for Dear Love"), break-up ("5:15"), alienation and romantic chaos ("Hurricane" and "Forgot to Laugh"), self-confidence ("Ready or Not"), self-esteem ("City Lights"), friendship ("We're Dancing"), money ("All I See Is Gold") and blonde girls ("Blonde").