Lautenberg, the oldest-serving member of the Senate and the last to serve in World War II, died "due to complications from viral pneumonia," according to a statement released by an aide.
Lautenberg's health had prevented him from appearing on the Senate floor much in recent months, and he had already decided not to run for reelection when his term ended in 2014.
N.J. Gov. Chris Christie, a Republican, will now be charged with appointing someone to the seat long-held by Democrats until a special election can be scheduled.
The state already has elections for governor and state legislature scheduled for Nov. 5, with primaries to be held Tuesday.
Newark Mayor Cory Booker, the only candidate who has so far declared to run for the seat next year, was considered a heavy favorite going into the race, but it is unclear how the special election might tip that race one way or another.
Lautenberg served two separate stints in the Senate, the first from 1982 until 2001, when he announced his retirement. He returned a year later to win the 2002 election after Sen. Bob Torricelli dropped out while facing federal corruption charges.
While in office, Lautenberg was responsible for the bill that banned smoking on commercial flights, which paved the way for smoking bans in restaurants and other public places. He pushed for stricter laws against driving while impaired and led the charge to raise the legal drinking age to 21.
He was known as a vocal critic of the Iraq War.
He went to Columbia Business School on the GI Bill after returning to home from serving in the Signal Corps in England, France and Belgium.
He defeated blood cancer in 2010. Lautenberg is survived by his wife, Bonnie Englebardt, and his four children from his first marriage.
Exploding whale video goes viral on Internet
Gal Gadot cast as Wonder Woman for 'Batman vs. Superman'