One of Solondz's short films, Schatt's Last Shot, was made in 1985. The title character is a high schooler who wants to get into Stanford, but his gym Teacher hates him. The Teacher fails him because he cannot make a shot in basketball. He has no luck with the girl of his dreams, but he wishes he was more like the coach, whom he challenges to a game of one-on-one.

In 1989 Solondz wrote and directed Fear, Anxiety & Depression, an episodic comedy about fledgling Playwright Ira (played by Solondz) and his frustrating interactions with the opposite sex. The film contains several musical interludes, including three songs written for the film. Stanley Tucci appears in one of his earliest roles as an old, disliked acquaintance of Ira's, who takes up playwriting on a whim and becomes the toast of Off-Broadway.

During the early 1990s, Solondz worked as a Teacher of English as a second language to Russian immigrants in New York City, and has described the experience as positive.

The frustrations of his first feature led Solondz to swear off further involvement with the industry. More than five years later, an attorney friend urged Solondz to give filmmaking another go, and promised partial Finance for any project Solondz came up with. The end result was 1995's Welcome to the Dollhouse, which went on to win the Grand Jury Prize at the Sundance Film Festival. The dark comedy follows the travails of Dawn Wiener, a bespectacled, toothy, and shy 7th-grade girl who is mercilessly teased at school and treated to alternating contempt and neglect at home. It was distinct from most earlier films about adolescent abuse due to its complex characterization. It gave a balanced and sometimes sympathetic portrayal of the bully antagonist Brandon, and its depiction of Dawn, the ostensible protagonist and victim of the story, showed her as deeply flawed and sometimes cruel. The film was a major success among critics, and a moderate success at the box office. It was a festival hit, with screenings all over the world.

Solondz's next piece was Happiness (1998), a highly controversial film due to the themes explored in it, which range from rape, pedophilia, suicide and murder to a bizarre sexual phone caller. After the original distributor October Films dropped it, the film was distributed by Good Machine Releasing. The movie received numerous awards, including International Critics' Prize at the Cannes Film Festival, and yielded strong critical praise for Solondz.

In 2001, Solondz released Storytelling, which premiered at the 2001 Cannes Film Festival. It is a film separated into two parts, entitled "Fiction" and "Nonfiction." The two stories share two thematic elements, but deal with each in an autonomous manner. Solondz used this format because he wanted to "find a fresh structure, a fresh form, and a different way of tackling what may be identical geographical material." When Solondz initially presented the film to the MPAA, he was told that if he wished to receive a rating other than NC-17, he would have to remove a scene of explicit sex involving a white female and a black male. However, a clause in Solondz's contract allowed him to cover part of the actors with a bright red box. "For me it's a great victory to have a big red box, the first red box in any studio feature [...] it's right in your face: You're not allowed to see this in our country." Solondz did, however, remove a portion of the film (which has variously been reported as either a subplot of the second story, or a third story entirely) which contained a sex scene involving two male actors (one of whom was James Van Der Beek).

Solondz's next film, Palindromes (2004), raised the eyebrows of many pundits and reviewers due to its themes of child molestation, statutory rape and abortion. The film was financed largely by the filmmaker. Like all of Solondz's previous films, Palindromes is set in suburban New Jersey. It was released unrated in the US.

In 2007, Solondz was honored with the Filmmaker on the Edge Award at the Provincetown International Film Festival.

On December 19, 2009, Solondz joined as adjunct professor the New York University's Tisch School of the Arts; he alternates semesters between New York's main campus of the school, and the grad film sister program at the Tisch Asia campus in Singapore. He teaches Directing and Writing the Feature.

In July 2010 Solondz completed the script of his next film, Dark Horse, which was filmed in Fall 2010. To Solondz's surprise, the Creative Artists Agency has appreciated the script, the first time for a movie of his. Solondz commented that he realized this is because "there's no rape, there's no child molestation, there's no masturbation, and then I thought, 'omg, why didn't I think of this years ago?'"

On September 5, 2011, Dark Horse was presented at the Venice Film Festival. On October 14, 2011, Dark Horse made its European premiere at the BFI London Film Festival. The film received a mixed reception. On April 23, 2012, Dark Horse was announced as the Closing Night selection for Maryland Film Festival 2012.

Wiener-Dog premiered at Sundance 2016. The film tells the story of a dog, as she travels from home to home. Amazon purchased the film at the festival.