Joey has a career in acting. He briefly mentions to the gang that Al Pacino is his idol. Joey also has the 1983 Scarface poster in his apartment room which featured Al Pacino. He also pursued modeling at one point. It was successful until he learned his latest picture was that for a health safety poster advertising VD. The poster was shown all over the city, including the scoreboard at Madison Square Garden and led to him being briefly ostracized by his friends, and even his whole family. His character is known for his simple-mindedness, trouble with understanding negative criticism of his acting (even once believing a description of his performance as "abysmal" was positive), love of food (particularly meatballs sub sandwiches and the world's famous Joey's Special... two pizzas) and success with women, which generated the popular catchphrase "How you doin'?" (his pickup line). However, he is something of an idiot savant in matters of romance. This is directly alluded to in the episode "The One Where Ross Dates a Student", when Chandler, referring to Joey, says "A hot girl's at stake and suddenly he's Rain Man." In another example, Joey made up an anecdote that Chandler and Monica referred to as the Europe story; apparently, anyone who hears it will immediately want to have sex with the teller. ("The One with the Videotape")

His roles varied from doctor to headshot in the above-mentioned public health poster for VD and even being a one time butt double. Joey's most famous acting role (and longest lasting) was as Dr. Drake Ramoray on the serial drama Days of Our Lives. However, when he claimed in an interview that he wrote many of his own lines, the writers of the show became annoyed and killed him off a few episodes later (he fell down an elevator shaft). His character later returned after a bizarre plot line resurrected him. In Season 7, he was up for a Soapie for Best Returning Male Character. He lost, so he tried to steal one. Joey's agent was Estelle Leonard.

Joey was also employed (briefly) at Central Perk as a waiter. Facing a dry spell in his career as an actor, Joey was persuaded by Gunther to take a job serving coffee. At first Joey tried to hide the fact of his new job from his friends, but they eventually figured it out. He did not like the work but, true to his nature, soon found a way to use his position to meet and ingratiate himself to attractive women by giving them free food, a practice to which Gunther quickly put a stop. He didn't take his job very seriously and spent a lot of his working hours sitting and talking to his friends. Eventually he was fired for closing the coffee house in the middle of the day to go to an audition while Gunther was running a personal errand. Rachel later persuaded Gunther to give Joey back his job, but once he found more steady acting jobs he eventually just stopped showing up. His absence was barely noticed.

Another one of Joey's careers when he was low on money was a sperm donor. He was donating for an experiment a hospital was having and as payment at the end of 2 weeks the hospital would give any donors a 700 dollar check. This was later mentioned when Monica was trying to get over her break up with Richard Burke. She decide she wanted a baby so she was looking for sperm donors and realized that one of the applicants was Joey.