Adler was born Charles Michael Adler on October 2, 1956 in Paterson, New Jersey. His family moved to Massachusetts in the mid-1960s. His sister Cheryl Adler is a psychotherapist who wrote the book "Sober University". Growing up Charlie Adler was a "TV junkie", a fan of The Three Stooges, Rocky and Bullwinkle and Irene Ryan's Granny Moses from The Beverly Hillbillies.
His first professional acting job was in a commercial in 1971. After that, he took a break from acting. During this time, Adler worked a variety of jobs, including waiter, janitor, paper delivery man, floor stripper, house painter, remedial reading teacher and caretaker for an Episcopal church.
In 1984 and 1985, he starred as Arnold Beckoff in Torch Song Trilogy, for which he was nominated for the 1985 Helen Hayes Best Actor Award, in New York, before moving to California in 1986.
His first animation role was recorded in New York, voicing Spike the Dragon in the My Little Pony television movie Rescue at Midnight Castle.
In 1985, after convincing the head of the Abrams, Rubiloff and Lawrence agency to allow him to audition for their voice over department, he went to a private audition for Ginny McSwain and Arlene Thornton. An agent had praised him in front of them as "the next Frank Welker." Despite the fact that McSwain recalls that he blew their minds, Adler recalls them having "no interest in him". Having no demo, they arranged for him to record an audition. Charlie Adler improvised characters on the spot during the tape, which impressed both McSwain and Thornton, however left him so embarrassed with his behavior that he performed with his back to them and his face hidden with a hat and sunglasses.
His voice acting career had taken off with a bang, Adler landed the roles of Nat Smurfling on the fourth season of Hanna-Barbera's Smurfs, Rowdy Roddy Pipper on Hulk Hogan's Rock 'n' Wrestling, Silverbolt on The Transformers and the unsympathetic role of Eric Raymond, the main villain on Jem.
After playing the transvestite Ralph/Rita in the short-lived sitcom The Redd Foxx Show, he was completely dissatissfied with working on a TV series and how "you spend your whole life going, 'God, I just want to be in a TV show and have a parking space'. Then I got it and it was just so not what I wanted to do." That is when animation "grabbed him".
He became active chiefly in animation, his roles include reprising Spike in the My Little Pony television series, Low-Light in G.I. Joe, the semi-regular role of Mr. O'Greasy in A Pup Named Scooby-Doo, Deputy Fuzz and Ted Hex in Bravestarr, Captain Caveman's son Cavey Jr. in The Flintstone Kids, Pinky Dalton in The Good, the Bad, and Huckleberry Hound, Quark and Zappy in Rockin' with Judy Jetson, The Hamburglar in a few McDonald's commercials, Mad Dog, Hacksaw and Howard Huge in TaleSpin, Dripple in Tom and Jerry Kids, and the sympathetic title character, The bear from darkest Peru in Hanna-Barbera's version of Paddington Bear.
In 1990, he lent his voice to Buster Bunny on Tiny Toon Adventures. During Season 3 when the staff started production on Animaniacs, Charlie was disappointed that he didn't get a recurring character on it, while minor voice-actors such as Frank Welker and Rob Paulsen from Tiny Toon Adventures were given main roles. He and his agent sent angry letters to Tom Ruegger and other producers, claiming that his treatment had been "shabby" and that he was going to leave the show. When Charlie dropped out, the studio still had a handful of episodes to record, so they re-cast the role of Buster with John Kassir. John's voice was slightly different than Charlie's; Adler's voice was rougher and more gravelly, whereas John's was smoother. John finished the last 10% of Charlie's lines from The Horror of Slumber Party Mountain. He performed Buster's voice in The Return of Batduck and It's a Wonderful Tiny Toons Christmas Special in 1992, Tiny Toons Spring Break Special in 1994, Night Ghoulery in 1995, and The Great Beanstalk video game in 1998. For the promos on Kids WB, Buster was played by various other voice actors. Charlie eventually returned to voice Buster for the unreleased video game, Tiny Toon Adventures: Defenders of the Universe! In 1993, he went on to portray Chance 'T-Bone' Furlong in Swat Kats: The Radical Squadron, which went on to be the number one syndicated show of 1994, Bill in The Terrible Thunderlizards, Ickis on Aaahh!!! Real Monsters, Ed Bighead, Bev Bighead and others on Rocko's Modern Life, Stalker Slaughter on Captain Planet and the Planeteers and Screwball Squirrel and reprising his role of Dripple on Droopy, Master Detective.
In 1995, he voiced several characters on multiple What a Cartoon! episodes, such as Gramps, Awfully Lucky, Yoink! of the Yukon and No Smoking. In the last one, he played Cow, Chicken and The Red Guy. No Smoking was a pilot created by David Feiss, which was greenlit to be a series in 1997 with Adler on board to reprise his characters, which now included a new character I.R. Baboon for a new segment within the show. The hit program Cow and Chicken ran from 1997-1999, receiving multiple awards and nominations, including an Annie Award for Outstanding Individual Achievement for Voice Acting in an Animated Television Production for Adler as Cow.
His voice directing career began in the late 1990s with Rugrats and continued with other Klasky Csupo franchises. Adler has since directed The Wild Thornberrys, All Grown Up, The Marvelous Misadventures of Flapjack, The Replacements and many more.
He also voiced Dr. Peacock in the Froot Loops commercials, Patrick Winks and Mr. Hornsby on Jakers! The Adventures of Piggley Winks, and SAVO on Danger Rangers and Mr. Whiskers in Brandy & Mr. Whiskers
In 2002, he directed his own short movie No Prom for Cindy in which he also played the title character. He was awarded the Palm Springs International Festival of Short Films Jury Award of Merit.
In 2007, he voiced in Michael Bay's live-action Transformers film series, providing the voice of Starscream after having voiced the characters of Silverbolt and Triggerhappy in The Transformers.
Just as Chris Latta voiced both Starscream and Cobra Commander in the Sunbow cartoons, Adler voiced Cobra Commander in G.I. Joe: Resolute and G.I. Joe: Renegades.
As of 2013, Adler is currently playing Professor Barney T. Hokestar in Ben 10 Omniverse and MODOK in Avengers Assemble and is also directing Bubble Guppies.
On the site Behind The Voice Actors he is chosen as the best voice for Buster Bunny, Super-Skrull, MODOK, Mojo, Cobra Commander, Low-Light, Stalker and Sunstorm.