A member of a prominent New Jersey family, Frederick Frelinghuysen was born in Millstone in 1817. His father, a prominent lawyer, died when Frederick was three, and Frelinghuysen was sent to Newark to live with his uncle, former New Jersey senator Theodore Frelinghuysen. He graduated Rutgers College in 1836 and entered the New Jersey bar in 1839, building a successful corporate law practice through the 1840s. Frelinghuysen entered politics in 1849 as a Whig and joined the Republicans during the election of 1860. He served twice in the United States Senate, finishing out the term of deceased senator William Wright from 1866 to 1868 and serving his own full term beginning in 1871.

He was one of a few Republican senators to vote in favor of Andrew Johnson's conviction during Johnson's impeachment proceedings. Frelinghuysen supported the Stalwart wing of the Republican Party that sought a third term for President Ulysses S. Grant in the 1880 election over the eventual GOP nominee, James Garfield.

After Garfield's assassination, Stalwart Chester Arthur selected Frelinghuysen to replace James Blaine as secretary of state in 1881. During his tenure, Frelinghuysen initiated few policy initiatives. He reversed much of Blaine's Pan-American diplomatic efforts and brokered a border deal with the Canadian government. Frelinghuysen died in Newark only a few months after leaving office.