The premiere of "Phineas and Ferb's Christmas Vacation" garnered 2.62 million viewers during its debut on Disney XD, the most watched telecast in the channel's history (including Toon Disney) and the number three program of the night in all demographics. It received 5.2 million viewers for its debut on Disney Channel. It was the highest rated episode of the series to date and 5th highest for the week.

In 2006, after the Disney Channel accepted the show, Povenmire and Marsh turned their attention to the company's overseas executives. Instead of a normal script, the two drew out storyboards and played them in a reel. Povenmire voiced over the reel with his dialogue and added sound effects. This novel approach secured the executives' support.

The first episode, "Rollercoaster", garnered a total of 10.8 million viewers when aired as a preview on August 17, 2007, holding onto more than half the record-setting audience of its lead-in, High School Musical 2. When Phineas and Ferb officially debuted in February the next year, it proved cable's number one watched animated series premiere by "tweens". Throughout the first quarter that followed, it peaked as the top-rated animated series for ages 6–10 and 9–14, also becoming number three animated series for all of cable television for viewers age 6–10. By the time the commissioning of the second season was announced in May 2008, the series had become a top-rated program in the 6–11 and 9–14 age groups.

The title sequence music, originally named 'Today Is Gonna Be a Great Day' and performed by the American group Bowling for Soup, was nominated for an Emmy award in 2008. The creators originally wrote a slower number, more like a "classic Disney song", but the network felt changes were needed to appeal to modern children and commissioned a rock version which made the final cut.

The United Kingdom Disney Channel has aired a series entitled Oscar and Michael's Phineas and Ferb Fan Club Show in homage to the animated series. The show features two boys who attempt to be like Phineas and Ferb by taking part in adventures to alleviate boredom. The series aims at educating kids and promoting activity and creativity. It entered its second season on April 10, 2009. The television series Psych has made references to Phineas and Ferb in its sixth season. In the episode "Shawn Rescues Darth Vader," main character Shawn Spencer (portrayed by James Roday) states that he learned his British accent from the granddad on Phineas and Ferb (he tells this to guest star Malcolm McDowell, who also happens to voice the granddad). And in "The Amazing Psych Man & Tap-Man, Issue #2," Shawn once again name-drops the series, stating: "I'm missing a Phineas and Ferb marathon. Perry the Platypus. He's a real platypus."

On March 3, 2010, a Disney press release announced a made-for-television film, based on Phineas and Ferb entitled Phineas and Ferb the Movie: Across the 2nd Dimension. It aired on the Disney Channel on August 5, 2011. The film concerned Phineas and Ferb accidentally helping Dr. Doofenshmirtz with an invention of his, which takes them to a parallel dimension. There, Perry reveals his double life as a secret agent to them, and, to save their friends from an alternative Dr. Doofenshmirtz, who is far more devious and threatening than his prime counterpart, they team up with their alternate dimension selves to stop him.

Disney produced a live-action talk show where the two characters (as cartoons) interview celebrities, similarly to Space Ghost Coast to Coast, which began airing in December 2010 as a two-minute talk-show format, featuring real-life celebrities such as Tony Hawk, Randy Jackson, Neil Patrick Harris, Seth Rogen, Taylor Swift, Andy Samberg, Tom Bergeron, Emma Roberts, Jack Black, Regis Philbin, Howie Mandel, David Beckham and Guy Fieri. The show ended on November 25, 2011.

In 2012, it was announced that a crossover between Phineas and Ferb and Marvel Entertainment, would air in the summer of 2013, titled Phineas and Ferb: Mission Marvel. It features Marvel Comics superheroes Iron Man, Spider-Man, the Hulk and Thor and the villains the Red Skull, Whiplash, Venom and M.O.D.O.K.. It is the first major animated crossover between Marvel and Disney since the acquisition of Marvel Entertainment by Disney in 2009.

In 2013, Disney commissioned Majesco Entertainment to create the newest Phineas and Ferb video game, which released in August 2013, entitled Phineas and Ferb: Quest for Cool Stuff, which is available on Xbox 360, Wii U, Wii, Nintendo 3DS and Nintendo DS.

In July 2013, the producers announced a Phineas and Ferb/Star Wars crossover which was used as a sidebar to the events of Episode IV: A New Hope. The special aired on July 26, 2014.

On May 7, 2015, Disney officially announced that the series has wrapped up after four seasons, and the final hour-long episode titled "Phineas and Ferb: Last Day of Summer" would premiere on June 12, 2015 on Disney XD, simulcast on Disney Channel. A 73-hour marathon of the show would begin on Disney XD on June 9, 2015. The series officially ended on June 12, 2015 on Disney Channel and Disney XD. It was also announced that a stand-alone hour-long special titled "O.W.C.A. Files" would be released the following Fall. The special officially premiered on Disney XD on November 9, 2015.

Alan Sepinwall and Matt Zoller Seitz gave a positive assessment for Phineas and Ferb in their 2016 book titled TV (The Book), stating that "In television, formula often seems to come from a lack of imagination.... Phineas and Ferb though, managed at the same time to be wildly imaginative and slavishly formulaic, using its repetitive structure not as a crutch, but as a sturdy framework on which it could hang all kinds of fantastic new ideas." They further added that "the characters' awareness of that formula, and any deviations from it, quickly became one of the show's most fertile sources of humor."

Co-creator Dan Povenmire has said that he would like to do a crossover with his and Jeff "Swampy" Marsh's follow-up show, Milo Murphy's Law, which takes place in the same universe as Phineas and Ferb. On July 21, 2017, it was announced that the crossover is planned to be broadcast in 2018. Before this crossover airs, a character from Phineas and Ferb, Dr. Heinz Doofenshmirtz, cameoed at the end of the episode "Fungus Among Us".