The Coliseum originally had a capacity of 13,000 to 15,000 depending on the event, and in the early 1980s the maximum capacity was increased to around 18,000. Before closing for renovations in 2015 the Coliseum seated 16,170 for hockey, up to 18,511 for concerts and 17,686 for boxing. Those renovations resulted in drastically reduced capacities: 13,917 for hockey and 16,500 for basketball.
The Coliseum was home to the New York Nets of the American Basketball Association, and later the National Basketball Association, from 1972 to 1977. The first event at the Coliseum was a Nets game against the Pittsburgh Condors on February 11, 1972.
The Nets won two ABA Championships in the Coliseum, with Hall of Famer Julius Erving headlining the team. In 1973–74 the Nets defeated the Utah Stars in five games to capture their first title. The Nets then captured the final American Basketball Association Championship in 1976, defeating the Denver Nuggets in six games. Following the 1976 season the Nets joined the National Basketball Association as part of the ABA–NBA merger.
After their first season in the NBA, the Nets moved to New Jersey. The New Jersey Nets played four seasons at the Rutgers Athletic Center before completion of the Meadowlands Arena at the Meadowlands Sports Complex.
The Coliseum also hosted the New York Arrows and later the New York Express of the original Major Indoor Soccer League. The Arrows, which existed as a franchise from 1978 to 1984, won the first four MISL championships. The short-lived New York Express played part of the 1986–87 season, ending operations before the All-Star break with financial troubles and a 3-23 record.
In NCAA Division I men's college basketball, the Coliseum hosted the ECAC Metro Region Tournament organized by the Eastern College Athletic Conference (ECAC) in 1978, 1979, 1980, and 1981. It also has hosted first- and second-round games of the NCAA Division I Men's Basketball Tournament in 1982, 1994, and 2001.
The New York Sets of World Team Tennis played their first match at Nassau Coliseum on May 7, 1974, and won the WTT championships in 1976. The team changed its name to the New York Apples for the 1977 season, and played 12 of its 22 home matches at Madison Square Garden and the Felt Forum, repeating as champions. Prior to the 1978 season, the Apples announced that they would leave the Coliseum and play all their home matches in the Madison Square Garden complex.
The New York Raiders, intended by the fledgling World Hockey Association to be their flagship franchise, was slated to play in the new Nassau Coliseum in 1972–73. However, the Nassau County government did not consider the WHA a fully professional league and wanted nothing to do with the Raiders. Nassau County retained William Shea to get an NHL team to play in the new building. The NHL responded by hastily awarding a franchise to Long Island—the New York Islanders—which forced the Raiders to play in Madison Square Garden, in the shadow of the New York Rangers. On October 7, 1972, the first Islanders game in Nassau Coliseum was played as the Atlanta Flames visited the Islanders. Flames forward Morris Stefaniw scored the first NHL goal in the building at 6:56 of the first period, while Ed Westfall scored the first goal for the Islanders, as the Flames won the game 3–2. The first Islanders' home win at the arena was on October 12, 1972, where they defeated the Los Angeles Kings 3–2. The Islanders' first playoff win at the arena came on April 20, 1975, where they defeated the Pittsburgh Penguins 4–2. On April 22, 1976, the Islanders earned their first playoff series victory at the arena by defeating the Buffalo Sabres 3–2, and winning the series 4–2.
On February 8, 1983, the arena hosted the 35th National Hockey League All-Star Game, during which Wayne Gretzky scored four goals in the third period and was honored as the game's most valuable player.
The Islanders were 11–1 in Stanley Cup Finals games at the Coliseum. Their only loss was a 1–0 setback in Game 1 in 1984 to the Edmonton Oilers. Islanders fans nicknamed the arena "Fort Neverlose" in honor of the team's strong home record during the finals.
The Coliseum was home to the New York Saints of the National Lacrosse League from 1989 to 2003. In 2007, it was home to four of the New York Titans National Lacrosse League team's eight home games (along with Madison Square Garden).
The Nassau Coliseum hosted minor league hockey prior to the awarding of the Islanders franchise, an event that was brought back in 2005, when the Islanders-affiliated Bridgeport Sound Tigers of the American Hockey League (AHL) played two "home" games at the Coliseum in the absence of NHL hockey due to the 2004–05 NHL lockout. On April 17–18, 2009, the Sound Tigers played two of their home playoff games against the Wilkes-Barre/Scranton Penguins at the Coliseum due to a scheduling conflict at the Arena at Harbor Yard in Bridgeport, Connecticut, the team's home.
In 2000 and 2005, the Professional Bull Riders brought their Built Ford Tough Series (originally Bud Light Cup) to the Coliseum.
On February 24–25, 2006, the Coliseum hosted the 44th NYSPHSAA Wrestling Championships. It was just the third time the annual event has been held on Long Island. Selling 17,755 tickets over three sessions, it broke (and still holds) the NYSPHSAA wrestling tournament attendance record.
On April 25, 2015, the final Islanders game at Nassau Coliseum was held, Game 6 of their first round playoff series against the Washington Capitals. The game was won by the Islanders 3-1, forcing a Game 7 in Washington. Islanders' Nikolay Kulemin scored the final NHL game-winning goal at Nassau Veterans Memorial Coliseum at 10:33 of the third period, a wrist shot against Braden Holtby. The Islanders' Cal Clutterbuck scored the final NHL goal at the Coliseum, an empty net goal that put the Islanders up 3-1 at 19:07 of the 3rd period. However, the Islanders were denied entry into the second round of the playoffs as they lost Game 7 of the series to the Capitals in Washington two nights later, thus making Game 6 the final major-league sporting event held at the Coliseum until the Islanders return three years later.
On July 19–20, 2014, the Global RallyCross Championship raced at the Nassau Coliseum parking lot.
On November 5, 2015, the Nets announced their new NBA D-League team, the Long Island Nets, would play at the renovated Coliseum starting in 2017 (the team played their first season at their parent team's home, the Barclays Center).
On July 22, 2017, the Coliseum hosted UFC on Fox: Weidman vs. Gastelum.
In February 2018, the Coliseum hosted the New York Open, an ATP 250 men's tennis tournament replacing the long-running Memphis Open.
The seating capacity for hockey during the life of the arena has been:
- 14,665 (1972–1973)
- 14,865 (1973–1976)
- 15,317 (1976–1978)
- 14,995 (1978–1980)
- 15,008 (1980–1981)
- 15,230 (1982–1983)
- 15,850 (1983–1984)
- 16,002 (1984–1986)
- 16,270 (1986–1987)
- 16,297 (1987–2001)
- 16,234 (2001–2009)
- 16,250 (2009–2012)
- 16,170 (2012–2015)
- 13,917 (2017–present)