Ryan played one of the main characters, Bailey Pickett, on the Disney Channel Original Series, The Suite Life on Deck, which is a sequel/spin-off to the hit Disney Channel series, The Suite Life of Zack & Cody. The series's pilot aired on September 26, 2008 in the US  and drew in 5.7 million viewers, and it became the most watched series premiere in Canada on the Family channel. The series was 2008's #1 top scripted television series for children between the ages of 6 to 11 and pre-teens between the ages of 9 to 14, beating the veteran series Hannah Montana and Wizards of Waverly Place in the ratings. The series was also 2009's top rated scripted series in the children and tween demographic (6-14), outpacing Hannah Montana and several other teenage shows.
In 2009, it was announced that Ryan landed a starring role in the independent feature film, What If..., alongside Kevin Sorbo and Kristy Swanson. The film was shot in Grand Rapids and Manistee, Michigan in July 2009 and was released in theaters on August 20, 2010. The film is produced by Pure Flix Entertainment and centers on a Christian family. In October 2009, Ryan hosted the first Tween Girl Summit Music Festival. "Tween girls are drawn to talented performers who emanate the joy of life, and we are so happy to have teen favorite Debby Ryan as the first host of The Tween Summit Music Festival," said Denise Restauri, founder of The Tween Summit, AllyKatzz.com and AK Tweens. "The Tween Summit is a day of celebrating the excitement of youth and hope for the future. As my tween friends say,'This concert is going to Rock!'"
In 2010, she starred in the young adult film 16 Wishes, about a teenager named Abigail "Abby" Louise Jensen (Ryan) who has been planning for her sixteenth birthday party ever since she was a little girl with a list of secret wishes she wants to come true, and on the day of her 16th birthday, all of her wishes come true. 16 Wishes went on to become the most watched cable program on the day of its premiere on the Disney Channel and one of the most watched movies on television. In addition, the movie introduced Ryan to new audiences, such as the contemporary adult audience since the movie received high viewership in the adults demographic (18-34). Ryan noted that to prepare for her role in 16 Wishes, she watched numerous Brat Pack movies, most occasionally Sixteen Candles which she stated is very similar to 16 Wishes. When asked how she prepared for the role, she said "It's, at the end of the day it depends on the script. You can do a comedy and it's completely different than a different comedy. I watch a lot of movies. 16 Wishes, when I went up to do that I watched Sixteen Candles (rated PG) and a couple of coming-of-age films. I love Molly Ringwald. So getting into the feel of that. . .". Ryan starred in The Suite Life Movie, based on the show she had starred in. The show finished its run on May 6, 2011.
In March 2011, it was announced that Ryan landed her own Disney Channel series called Jessie, which debuted in September 2011. The show follows a girl who moves from Texas to New York to become a star but becomes a nanny instead for a family with four children. Jessie is a show she also helped create, relating that she wanted her character to relate to herself. In February 2012, she starred in another Disney Channel movie entitled Radio Rebel.
Ryan plays several instruments including the guitar, piano, and keyboard. She is also a songwriter and writes music alongside her older brother. Ryan has showed interest in several types of music and her music genres are mainly jazz and country pop with a blend of alternative rock. Ryan was set to headline the "Terrific Teen Tour", a concert series which co-headlined Mitchel Musso, Jasmine Richards and Savannah Outen, that would start on July 9, 2009 and end on July 14 but the tour was canceled due to schedule conflicts. The tour would have been Ryan's debut as a live musician. Ryan debuted her musical talents in The Suite Life on Deck episode, "Beauty and the Fleeced". She then went on to record songs for the movies 16 Wishes and Radio Rebel, both of which she starred in. She also recorded the theme song "Hey Jessie" from the Disney Channel Original Series Jessie, which she also stars in, and in a first-season episode performed the country single "Texas Guys".
Debby is releasing her new mixtape album on November 9, 2013 called Debby. She is now signed to Hollywood Records and is set to release her album next year.
In July 2012, Ryan started work on a clothing line for 2013. She said she was in the beginning stages of building herself a fashion brand and revealed that she has been looking into designers and interviewing brands she might like to work with.
In a 2009 People Magazine interview, Ryan stated that her Suite Life co-star, Brenda Song, is her acting idol. In a March 2009 interview, Ryan revealed she also looks up to Meryl Streep; Ryan claims Streep "is so profoundly thought-provoking and life-changing." Ryan has said that her other role models include Anne Hathaway, Rachel McAdams and Tobey Maguire. When asked about musical tastes, she has said, "I love jazz! I love singing it. I also love country! My brother loves rock; he also has this chill Jason Mraz-like style. So basically, my answer is: jazz-country-rock-alternative? I have no idea! But I honestly would love to make country music."
Debby is currently dating Cole Sprouse since March 2009.