Last call is at 4 a.m. in Buffalo, rather than 2 a.m. as in most other areas of the U.S. This is often attributed to the historically high density of industrial facilities and the demand of second and third shift patrons. It is also because New York law allows bars to be open until 4 a.m. (However, local municipalities can override it to an earlier time.) This law was actually designed to accommodate the thriving late nightlife of New York City, but the state's "Second City" has adopted it as well.

Several distinct and thriving nightlife districts have grown around clusters of bars and nightclubs in the city. The most visible nightlife district is West Chippewa Street[60], located between Main Street and South Elmwood Avenue. The area is home to high-energy dance clubs, crowded bars, trendy coffeehouses, and restaurants. Some of the most popular hot spots in Buffalo New York are: Coles, Mr. Good bar, Side Bar, Geckos, MT Pockets, Shadow Bar, Checkers. Allentown, where bars are as numerous but the atmosphere is a bit more relaxed, is a several minute walk north to Allen Street. Some of the bars on Allen street in bBffalo New York include, La Tee Da, Gabriel's Gate, Brick bar, Hardware, and sample bar/restaurant. Allen Street near Main Street houses several gay bars, while Allen near Elmwood has many bars that feature live music. Continuing up Elmwood Avenue from Allentown is the Elmwood Strip, which runs about two miles to Buffalo State College. This strip has numerous small boutiques and restaurants, with few large corporate establishments. Crowds on this strip include everyone from college students to families to the elderly.

The city and surrounding Niagara Region also have an active summer concert schedule, a large portion of which are free and easy to access. The events are well planned and are spaced out through the week. Artpark on Tuesday nights, Buffalo Place hosts 'Thursdays at the Square', The Canal Concert series is on Saturday nights in Lockport and new for 2008 is a Friday night series on the Erie canal in North Tonawanda.

Buffalo is home to over 50 private and public art galleries , most notably the Albright-Knox Art Gallery, home to a world-class collection of modern and contemporary art. The local art scene is also enhanced by the Burchfield-Penney Art Center, Hall walls Contemporary Arts Center, CEPA, and many small galleries and studios. American Style ranked Buffalo fourth in its list of America's top art destinations.

Two street festivals - the Allentown Art Festival and the Elmwood Festival of the Arts - bring thousands of people to the city to browse and purchase original crafts. The Buffalo Philharmonic Orchestra, which performs at Klein Hans Music Hall, is one of the city's most prominent performing arts institutions. Shea's Performing Arts Center, long known as Shea's Buffalo, is an old-style large theatre that continues to show productions and concerts. Buffalo is also home to the second largest free outdoor Shakespeare festival in the United States, Shakespeare in Delaware Park.