• Teddy Duncan (Bridgit Mendler), Charlie's only sister and the second-oldest Duncan sibling. Feeling that she will not be around as much when Charlie is grown, she produces and directs video diaries for her, hoping they will give her advice that will help her be successful as a teenager. She produces these video diaries at the end of every episode, and at the end of every video diary she says "Good luck Charlie".
• Amy Duncan (née Blankenhooper ) (Leigh-Allyn Baker), Bob's wife and the mother of PJ, Teddy, Gabe, Charlie, and Toby. She works as a hospital nurse and is often portrayed as dutiful, protective and comedic. It is revealed in the movie that she is pregnant again with her fifth child.
• Gabe Duncan (Bradley Steven Perry), the middle Duncan sibling, being both the younger brother of Teddy and PJ and the older brother of Charlie and Toby. He is initially disconcerted by Charlie's arrival and is the last one of the family to get used to her, until his older sister, Teddy, helps him. He is a prankster and troublemaker, (a rebellious teenager) and has a rivalry with their neighbor Mrs. Dabney, who is often the target of Gabe's pranks and stunts.
• Charlie Duncan (Mia Talerico), the title character and the second-youngest Duncan sibling. She is generally portrayed as being happy, but can also be mischievous at times. Many of the Duncan family's adventures revolve around Charlie.
• Bob Duncan (Eric Allan Kramer), the father of Teddy, PJ, Gabe, Charlie, and Toby, and husband of Amy. He owns a pest control company, "Bob's Bugs Be Gone".
• PJ Duncan (Jason Dolley), the eldest Duncan sibling. He and Teddy often fight, although they care about each other, and he usually gets along well with his younger brother Gabe. He often appears awkward, somewhat careless, and childish, but on numerous occasions has been known to be resourceful, creative, and intelligent. He has also been shown to be a good cook. He and his best friend Emmett have their own band entitled "PJ and the Vibe". In season three, PJ moves into an apartment shared with Emmett.
• Ivy Wentz (Raven Goodwin), Teddy's best friend, who is seen spending most of her time with Teddy at the Duncan's residence. She often accompanies Teddy on her dutiful, or personal, excursions.
• Mrs. Estelle Dabney (Patricia Belcher), the Duncans' strict and easily annoyed neighbor, who is often suspicious of Gabe, because his pranks and troublemaking are frequently directed towards her.
• Spencer Walsh (Shane Harper), Teddy's on-again, off-again boyfriend throughout the series, who she begins to date in the first season.

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Good Luck Charlie was created by Phil Baker and Drew Vaupen, who have been writing together since 1993 on shows ranging from Suddenly Susan to Sonny with a Chance. The pair aspired to create a program that would appeal to entire families rather than simply kids. Inspired by the success of reruns of shows such as Full House and George Lopez with young audiences, Vaupen and Baker turned to family sitcoms. "We wanted to do a show about a family, to bring back a family sitcom and make it about a real family, not wizards, nobody's a pop star, nobody has a TV show", said Vaupen, referring to Wizards of Waverly Place, Hannah Montana, and Sonny with a Chance. Veteran writer-producer Dan Staley (Cheers) later joined the show as executive producer. Disney's Gary Marsh said "because most network television abandoned the traditional sitcom, Disney has been able to snatch up a lot of experienced talent for behind the camera, including executive producer Dan Staley..."

The series was publicly announced in July 2009 with a press release announcing the first season order as well as the primary cast.

Good Luck Charlie's central family, the Duncans from Denver, Colorado, was carefully crafted for broad appeal. While the series is still told primarily through the view point of the Duncan children, the children's parents, Amy and Bob, are less on the periphery and writers attempt to add scenes that adult viewers can relate to. For example, in one scene in the pilot episode Amy confesses to Bob that she is overwhelmed with becoming a working new mother again. "She's not sure she can pull this off", says Bonnet. "And just playing that scene the way we did, a very real scene between husband and wife, kind of makes this show different". The writers also try to include jokes for adult viewers while remaining chaste enough for their young target audience. Unlike most previous Disney Channel series such as Sonny with a Chance, Hannah Montana, or Cory in the House, both parents are seen in the Duncan family. "It felt like the right time to have a show with two parents, to debunk the myth that Disney never has the mom in the picture", says Adam Bonnett, Senior Vice President of original programming for Disney Channel. "Because it is a myth".

Because a series about the rich and famous might alienate viewers in a troubled economy, the Duncans were made middle class. According to Gary Marsh, Entertainment President of Disney Channel Worldwide, "What we want to do is acknowledge the reality of the times in which we live, where two parents work, where kids are expected to help out around the house in meaningful ways. Real-life issues happen. Everyone isn't living 'The Life of Riley' all the time." Broadening Disney Channel's appeal was a concern when choosing the names of the characters and the title of the program. "You want a title that says, a) this is a sitcom and, b) this is something that will interest the main demographic but also we're trying to expand the Disney brand beyond just girls", Vaupen commented. The series' title was originally "Love, Teddy", the phrase Teddy had used to end her video diary entries during development. However, "Love, Teddy" immediately felt feminized and almost excludes boys", Vaupen said. "We also didn't want to have the word 'Baby' in the title because that would exclude certain people". The Duncan baby was originally named "Daisy" during development, but producers thought that "Charlie", which is generally a masculine name, would attract more boys.

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The series earned positive reviews. Robert Lloyd of The Los Angeles Times described it as a "professional sitcom from sitcom professionals" with efficient jokes and typical sitcom characters, and situations which are "willfully arranged". Lloyd praised the series for offering a "contextually novel picture of a teenage girl taking care of her baby sister with a persuasive nonchalance and practical ease that transcends the strenuous comedy that surrounds it". Neal Justin of the Star Tribune said the "slapstick heavy, laugh-track fueled sitcom" had no redeeming qualities other than "keeping your 11-year-old sedated for a half hour". Rob Owen of the Pittsburgh Post-Gazette said Good Luck Charlie would appeal to kids, but not adults. "Parents have seen the same sort of show done before and better in ABC's 1980s-era TGIF lineup", wrote Owen. Contrarily, Brian Lowry of Variety magazine said Good Luck Charlie was "a surprisingly refreshing throwback to ABC's "TGIF"-style sitcoms". He commented that while the series did not "push sitcom boundaries", it was "sprightly" and "pleasantly handled".

On June 20, 2013, Disney Channel announced that Season 4 Episode 19, "Down a Tree", would feature a married lesbian couple, making Good Luck Charlie the first Disney Channel series to do so. LGBT rights organization GLAAD as well as actresses Miley Cyrus and Evan Rachel Wood expressed their support and lauded Disney for the inclusion of the characters. By contrast, the One Million Moms division of the American Family Association protested and asked Disney not to air the episode. In a statement to TV Guide, a Disney Channel spokesperson stated that the episode was "developed to be relevant to kids and families around the world and to reflect themes of diversity and inclusiveness." Disney aired the episode as planned on January 26, 2014.
The series premiered to 4.7 million viewers, making it the highest-rated series premiere for a Disney Channel Original Series since The Suite Life on Deck in 2008, and the week's highest-rated cable program. Maclean's reported that overall, the first season "has been doing about as well as Disney's more successful shows – The Suite Life and so on".

On June 24, 2012, the episode "Special Delivery" became the most watched episode ever of Good Luck Charlie, earning 7.48 million viewers, surpassing the episode "Snow Show (Part 1)" which had 7.24 million viewers as well as the episode "Good Luck Jessie NYC Christmas" that garnered 5.8 million viewers and the series' pilot episode "Study Date" which had 4.68 million viewers. The most-watched episode of the series was "Special Delivery" with 7.5 million viewers. The least watched episode was "The Unusual Suspects" with 1.9 million viewers. The most viewed episode in the United Kingdom and Ireland was "Special Delivery" with 602,000 viewers when it aired on October 12, 2012.