Incumbent Democratic Senator Edward Murphy Jr. stood for re-election to a second term but was defeated by Republican Chauncey Depew.

Democrat Edward Murphy Jr. had been elected to this seat in 1893, and his term would expire on March 3, 1899.

Depew had been Secretary of State of New York from 1864 to 1865, and was the frontrunning candidate to succeed Thomas C. Platt at the U.S. Senate special election in 1881 when he withdrew after the 41st ballot.

Depew was re-elected in 1905, and served two terms, most of the time alongside his adversary of 1881, Thomas C. Platt.

In 1911, Depew was defeated for re-election by Democrat James A. O'Gorman after a deadlock of two months and a half.