The 133-year-old statue depicted General Robert E Lee, the top military leader in the Confederacy, crossing his arms as he faced north towards his old enemy.
Critics say monuments to the Confederacy are racially offensive, but supporters say they are important symbols of the city's Southern heritage.
The three other statues were all removed at night to limit clashes.
The workers on the job were wearing bullet-proof vests as well as masks.
In a statement on Thursday, New Orleans Mayor Mitch Landrieu said the condemned statues "were erected decades after the Civil War to celebrate the 'Cult of the Lost Cause', a movement recognised across the South as celebrating and promoting white supremacy."
Barricades went up overnight around the park where the 16ft (4.8m) statue was perched atop a 60ft column.
The cables for a nearby streetcar were also temporarily taken down to allow construction equipment into the park.
Before police cleared the area on Thursday, nearly 200 protesters gathered to voice support and opposition to the monument.
Demonstrations were mostly peaceful, local media report.
The only flashpoint was when a pro-removal protester snatched a Confederate battle flag.
One man was arrested for climbing on to the monument's pedestal and refusing to come down.
The monument to Lee was erected on 22 February 1884 - nearly 20 years after the Civil War ended.
On the day of the unveiling, a crowd of nearly 15,000 people came to watch, the Daily Picayune newspaper reported the next day.
At the exact moment that the statue was unveiled, a 100-gun salute was fired, and "a mighty shout went up from the soldiers of the Confederacy", the Daily Picayune reported.
City officials say the monuments will be moved somewhere such as a museum where they can be "placed in their proper historical context from a dark period of American history".
But WWL-TV has found the removed monuments to Confederate President Jefferson Davis and PGT Beauregard in a city-owned scrap yard.
Supporters of the monuments say they are a cultural legacy that promotes heritage rather than racism.
The decision to remove the statues came in December 2015, six months after a white supremacist shot dead nine black worshippers at a South Carolina church.

Dr Hill, who started to log runs on 20 December 1964, finished Manchester's 5km Heaton Park parkrun earlier.
The 76 year old, who lives in Hyde but grew up in Accrington, Lancashire, has competed in three Olympic Games and has won gold at the Commonwealth Games.
The distance recorded in his log book adds up to 160,000 miles, or running around the world more than six times.
After a "disastrous" Olympics in Tokyo, he said he started running daily to "get the best out of myself".
He said: "Once you get into the habit of it, you just do it. Just get wrapped up and get out the door.
"It's [my] advice to everybody - just start running and within five minutes you're in your stride and probably enjoying it."
Dr Hill was the first British runner to win the Boston marathon. In later years he went into business, setting up a sportswear company.
He set several world records during his career, including a 2:09:28 time at the 1970 Commonwealth Games marathon in Edinburgh.
The organisers of the Heaton Park parkrun said they were "honoured that he has chosen to celebrate this milestone with us".

The Spanish midfielder, 30, joined Watford from Fiorentina on a four-and-a-half-year deal in January 2016.
He played 17 times in all competitions during his first season.
But in August 2016 he moved to Valencia on a season-long loan, returning to Spain where he had previously played for Atletico Madrid, Valladolid, Mallorca and Celta Vigo.
Guizhou Hengfeng Zhicheng currently sit 11th of the 16 teams in the Chinese Super League after 16 games of the season.
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Masked city workers in New Orleans have removed the last of four monuments to the pro-slavery rebellion defeated in the US Civil War.
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Former Olympian Ron Hill has completed his ambitious goal of running at least a mile a day for 50 years.
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