In 1902, Vincenzo Crisci opened a grocery store in the front of the building where he lived with his family and sold quality foods he imported from Italy. When people he knew from the neighborhood stopped in, he'd usually offer them something to eat, like a bowl of soup or a dish of pasta. People loved the food, his tomato sauce in particular, the kind of which, with some bread, could be a meal on its own. From the popularity of the dishes he made, Vincenzo got the idea he could make a business of serving food. As he gradually removed more shelves and added more tables, the transition from a grocery store to a restaurant began. For years it was both, until an apartment on the second floor became available, and he moved his family up there, converting the whole downstairs into a restaurant. Vincenzo became even more respected in the neighborhood, and Crisci's survived the Great Depression to become a thriving business, gaining local renown through the quality of its food and word of mouth.

As Vincenzo grew older, his three sons, Charles, Philip, and Salvatore, got more involved in the business. When Vincenzo died in 1958, his funeral was a huge event in the neighborhood, with people from all around attending and long processions of cars full of flowers. The sons took over Crisci's and began building it up even more, such as with a second major renovation in the 1960s, and its reputation spread further beyond the neighborhood. The restaurant became an institution, and the days it served some special dish were events onto themselves, like braciole on Sundays.

Tight control was maintained on the quality of the food, from the preparation of the ingredients to the final dish. Pastas such as fettuccine, ravioli, and manicotti were all made with the finest soft wheat flour and eggs, and all butchering was done on site. The breads were purchased from a local bakery, where it was baked in coal-fired ovens. The tomato sauce was especially important as it formed the basis of many of the dishes. Whenever it was prepared by someone new, it had to be tasted and approved by Salvatore before it could be served, to make sure it was true to Vincenzo's original recipe. All the chefs specialized solely in Italian cooking, some of them having emigrated from Italy.

As its popularity and reputation continued to grow, famous actors and politicians began to frequent Crisci's. This would often create interesting scenes, such as Mafia captains and congressmen dining a few tables apart. Other times, events would culminate to make the usual vibrant and party-like tone of the restaurant almost magical. One such occasion is when the Mets won the World Series in 1986, with the exuberance of the patrons and the celebrities coming in, including Mets pitcher Jesse Orosco, creating this ineffable atmosphere.

The second generation beginning to get involved, Peter and Louis Crisci started working at the restaurant, assisting in the kitchen and waiting tables, learning how to keep the tradition, and eventually taking over the business completely.

Crisci's began to receive more media attention by the 1980s and achieved a number of favorable reviews, such as from the New York Times and Zagat Survey. It was even praised by other restaurants, such as Peter Luger Steak House, which would recommend Crisci's to its own customers looking for quality Italian food.

In 1994, the restaurant closed, but its spirit and legacy live on.