Jacob Collamer was born in Troy, New York. He graduated from the University of Vermont at Burlington, served in the War of 1812, read law, was admitted to the bar in 1813, and became partner to Judge James Barrett. He served four terms in the Vermont House of Representatives and from 1833 until 1842 was assistant judge of the Supreme Court of Vermont. Elected to the United States House of Representatives in 1842 as a Whig, he advocated the annexation of Texas, supported the Mexican-American War and the tariff, and received national recognition for his "Wools and Woolens" speech.

Collamer served as Postmaster General under President Zachary Taylor. He became a circuit court judge in Vermont from 1850 to 1854. In 1855, he was elected to the Senate as a conservative, anti-slavery Republican. Throughout his career in Congress, he concentrated on land and tariff issues. He defended his position even when in the minority, as exemplified in his vigorous minority report as a member of the Committee on Territories, chaired by Stephen A. Douglas. He was one of two senators who refused to vote for the Crittenden Amendment, which proposed resubmitting the pro-slavery Lecompton Constitution for Kansas to popular vote. Along with his colleague, James R. Doolittle of Wisconsin, Collamer represented the minority view for the so-called Mason Report (June 1860), prepared by the Senate committee which investigated the John Brown raid on Harper's Ferry of October 1859. Collamer opposed the Reconstruction Plan of President Abraham Lincoln, advocating congressional control instead. He had received the presidential nomination from Vermont in 1860 but withdrew after the first ballot.

From 1855 to 1862 he was the last president of the Vermont Medical College. Reelected to the Senate in 1861, he served until his death on November 9, 1865, at his home in Woodstock, Vermont.

In 1881, the state of Vermont donated a marble statue of Collamer to the U.S. Capitol's National Statuary Hall Collection.