Wood was born in Philadelphia, Pennsylvania and moved to New York City, where he became a successful shipping merchant. He was chairman of the chief young men's political organization in 1839 and was a member of the Tammany Society, which he used as a vehicle for his political rise. As a member of the Democratic party, he was elected to Congress in 1841 and served until 1843.

In 1854 Wood was elected mayor of New York City. The state legislature created the New York City Municipal Police in 1853, but during Wood's first term as Mayor (1855-1857). He was re-elected in 1857, when the New York gang the Dead Rabbits combed the city's cemeteries for names to add to the voter rolls.

In the 1856-57 session, the Republicans at Albany shortened Wood's second term of office from two years to one, and created a Metropolitan Police Force, with Frederick Talmadge as superintendent, to replace Wood's corrupt Municipal Police. Talmadge demanded that Wood disband the Municipal Police, but Wood refused, even in the face of a May 1857 decision by the Supreme Court. Superintendent George W. Matsell, 15 captains and 800 patrolmen of the Municipal Police backed Mayor Wood.

Captain George W. Walling pledged his loyalty to the new Metropolitan Police and was ordered to arrest Mayor Wood. Wood refused to submit and when Captain Walling attempted force, New York City Hall was occupied by 300 Municipal policemen, who promptly tossed Captain Walling into the street. Fifty Metropolitans in frock coats and plug hats then marched on City Hall with night sticks in hand. The Municipals swarmed out and routed the Metropolitans. Fifty-two policemen were injured in the police riot.

The Metropolitan Police Board called out the National Guard, and the Seventh Regiment surrounded City Hall. A platoon of infantry with fixed bayonets marched into City Hall and surrounded Mayor Wood who then submitted to arrest. Mayor Wood was charged with inciting to riot, released on nominal bail and returned to his office.

The feud continued on through the summer of 1857, with constant confrontations between the rival police forces. When a Municipal arrested a criminal, a Metropolitan would come along and release him. At the police station, an arresting officer would find an alderman and a magistrate from the opposing side waiting. A hearing would be held on the spot and the prisoner released on his own recognizance.

The gangs of New York had a field day. Pedestrians were mugged in broad daylight on Broadway while rival policemen clubbed each other to determine who had the right to interfere. Soon the gangs were looting and plundering without interference, but turned on one another in turf wars, which culminated in the Fourth of July gang battle. The Dead Rabbits, the Plug Uglies and several other Five Points gangs marched into the Bowery to do battle with the Bowery Boys and to loot stores. They attacked a Bowery Boys headquarters with pistols, knives, clubs, iron bars and huge paving blocks, routing the defenders. The Bowery Boys and their allies the Atlantic Guards poured into Bayard Street to engage in the most desperate and largest free-for-all in the city's history. The Metropolitans attempted to stop the fighting but were severely beaten and retreated. The Municipals said the battle looked like a Metropolitan problem and was none of their business.

Fernando Wood served a second mayoral term in 1860 -62. Wood was one of many New York Democrats sympathetic to the Confederacy, called 'Copperheads' by the staunch Unionists. During his second mayoral term in January 1861, Wood suggested to the City Council that New York City secede and declare itself a free city, to continue its profitable cotton trade with the Confederacy. Wood's Democratic machine was concerned to maintain the revenues (which depended on Southern cotton) that maintained the patronage.

Wood's brother Benjamin Wood purchased the New York Daily News in 1860, supporting Stephen A. Douglas, and was elected to Congress, where he made a name as an opponent of pursuing the American Civil War.