Between finding ways to rebel against his family and being the butt-end of anti-Semitic jokes by rednecks, the young social outcast eventually learned to channel his anger and frustration into comedy.
In the past year, 26-year-old Mandel has appeared on "The Late Late Show With Craig Ferguson" and toured with Israeli hip-hop star Subliminal as part of Taglit-Birthright Israel's "Israelity." The up-and-comer also took the top spot in Comedy Central's first "Open Mic Fight" contest in September, which pitted 72 comics against one another.
In the coming months, he's slated to appear on the third season of Comedy Central's stand-up showcase, "Live at Gotham."
On the outside, things look pretty promising for Mandel. He's moved from rural California into urban Los Angeles, he has friends and he's found his comedic voice on the road and with the help of family.
But on the inside, he's generally irritated with the world. As a newly minted Angeleno, Mandel believes a city full of smog, traffic, superficiality and an increasingly high cost of living will safeguard him from ever running out of material.
"People in L.A. talk about [succeeding in the entertainment industry] but don't actually do anything about it," he observed.
While his low threshold for annoyance might inspire the tone of his delivery, his routine has also become more catharsis than mere outlet for complaint.
"[Stand-up] is my saving grace," he declared, adding that his humor is more diagnostic than a simple whine.
Born Mohahn Mandelbaum, his father picked his name thinking it was Jewish. During the bris the mohel pointed out it wasn't a Jewish name, but his parents decided to stick with it even after they discovered Mohahn was Hindu.
Mandel says he developed an interest in comedy at an early age.
"My parents used to laugh at everything I said when I was a kid," he said. "They thought it was hilarious. But really maybe that's just because they're hippies and they smoked a lot of weed," he says in his routine.
His main comedy influence as a child was his older cousin, Sue Kolinsky, a professional stand-up comedian at the time, as well as a producer for "Newlyweds: Nick and Jessica" and a segment producer of "The Osbournes."
During her visits, Mandel tried to continuously "out-funny" his cousin, but he eventually settled on the title "second funniest in the family."
Mandel went on to study creative writing at UC Santa Barbara, where he wrote stories and even a novel, but gave up because he was "sick of writing things that no one ever read," he said.
Recalling his cousin's success in comedy, Mandel decided to give stand-up a try. A few unsuccessful joke-writing sessions followed and he felt deflated.
His turning point came as a post-grad, reflecting on an evening of drunken embarrassment. Frustrated by his own immature behavior from the night before, Mandel scribbled a few words on a napkin while at breakfast: "Does anybody know that guy that goes to parties and gets drunk and obnoxious ... great, so I don't have to introduce myself."
From that point on, Mandel said he became obsessed with writing jokes.
After he graduated, Mandel spent six months perfecting his routine in London. He found British audiences difficult to appease at first, but broke through when he started joking about America and President Bush.
When he returned to the States, Mandel went on to win third place in the 2006 San Francisco International Comedy Competition, which led to his recent victory on Comedy Central.
Mandel and his cousin now share a loose protege-mentor relationship; Mandel occasionally asks Kolinsky for advice about material and she responds with comments.
"Ever since he was a kid, he's always looked up to me for professional advice," Kolinsky said. "But he's done this all on his own."
While he enjoys the success, he finds life on the road lonely. Mandel spends much of the time by himself as he waits in each hotel room before each performance.
"On the road, you're by yourself so much; so much time to think about everything," he said. "You sit around in the hotel for 14 hours and you perform for 45 minutes."
When he's backstage before a performance, Mandel deals with another irritation -- he's regularly gripped by anxiety and contends with an upset stomach. It's a nightly malady that disappears as soon as he grabs the mic.
For Mandel, performing in front of 200 people is more comfortable than talking face to face with someone. He considers stand-up a complete high, better than sex.
"Unless you combine the two," he said.
Mo Mandel performs with The Masters of Comedy at The Improv Olympic, April 6, 7:30 p.m. $5. For more information, call (323) 962-7560 or visit www.momandel.com.