To promote awareness and entice viewership, Muppet moguls staged a "real-life" divorce between Kermit and Miss Piggy. It made headlines on such news outlets as CNN.

A ten minute "Muppets" mockumentary was shown at the 2015 San Diego Comic-Con. This mockumentary was the reason ABC ordered a full series.

Eric Jacobson (performer of Miss Piggy, Animal, Fozzie, and Sam) also performed the characters Grover and Bert (among others) on Sesame Street (1969). These characters were all originated by Jim Henson and Frank Oz, and performed by Oz.

Jim Henson was the original puppeteer and voice of Kermit. After Jim's death in 1990, Steve Whitmire, who joined the Muppets back in 1978, accepted an offer from Jim's son Brian Henson, to take over as Kermit the Frog. Steve portrayed Kermit from 1990 until October 2016, when he was fired from the role by Disney, partly due to Whitmire having irked showrunners during production of this series, by providing detailed notes over what the Muppet characters would and would not do. Matt Vogel was then handed the role of Kermit after Whitmire's departure.

In episode two, "Hostile Makeover," the character Lips has a brief line of dialogue. He is the horn player in the Electric Mayhem Band. While featured in previous Muppet television and film projects, he has never spoken before that.

Some viewers were shocked to hear Miss Piggy and Kermit the Frog broke up for the 2015 series, but older fans may not be surprised. On May 4, 1990, Jim Henson's last appearance was on The Arsenio Hall Show (1989) season two, episode one hundred forty-four, "Episode #2.144." When asked about Piggy, Jim puppeteered Kermit and had Kermit say that things between himself and Piggy were not going too well, and that her celebrity lifestyle was contributing to them drifting apart. Jim died afterwards on May 16, 1990. The new 2015 show opens by showing viewers Kermit had a last straw moment because of her celebrity lifestyle and Kermit broke up with her.

Tom Bergeron was officially the first guest star in episode one, "Pig Girls Don't Cry." Technically, that honor goes to Elizabeth Banks, who appeared in the 11-minute pilot that was pitched to ABC for executives to see its potential. Topher Grace also appeared.

In each week's opening, after the other Muppets take all the food in the break room, Kermit says "It's time to get things started." This was a line in the original Muppet Show opening song. "It's time to play the music. It's time to light the lights. It's time to get things started, on The Muppet Show tonight."

The Muppet Show (1976) was seen in one hundred eight countries. Disney Media Distribution confirmed that the new show had been picked up by stations in one hundred twenty-two countries and territories. Locations include the UK, Ireland, Italy, Denmark, Greece, Vietnam, South Africa, China, Australia, New Zealand, Pakistan, Russia, and the Middle East.

Guest star Josh Groban appeared in Muppets Most Wanted (2014).

The show premiered September 22, 2015 with 9.01 million viewers Live+SD for adults between eighteen and forty-nine years old. Three days later, the Live+3D results for eighteen to forty-nine-year-olds came in at 11.1 million viewers for this show. This made this show the number one rated comedy premiere in a year, and, the number two new television series overall amongst young adults, behind the adult drama Blindspot (2015).

In episode twelve, "A Tale of Two Piggies," Miss Piggy suffers a wardrobe malfunction, which, Sam the Eagle tells Kermit, prompts the "One Million Angry Parents Association" to protest Up Late with Miss Piggy. This is a reference to the real-life protest staged against this show by the group One Million Moms, which deemed the series "unsuitable for family viewing" months before it even started airing.

This is the only series where Miss Piggy never gives a single karate chop to anyone.

The show was cancelled after only one season, due to ratings being lower than expected.

In the early part of episode four, "Pig Out," Fozzie is giving a behind-the-scenes monologue. The Swedish Chef is in the background, licking doughnuts on the catering table and putting them back. In the early part of episode ten, "Single All the Way," Chef does it for a third time this season, but with a Christmas cookie. Chef licks the cookie and puts it back down just as Fozzie approaches to talk to Chef. This is a reference to Ariana Grande, who was known for such behavior.