D'Amato went on to win a plurality in the general election over Elizabeth Holtzman and Javits, who remained in the race as the candidate of the Liberal Party of New York.

[2] For years, Javits had been considered politically "invincible," but had become vulnerable in 1980 in part due to the rise of the Conservative Party of New York,[2] which had cut into the Republican base.

However, amid widespread speculation that he would not run, two challengers entered the race: Queens attorney James Eagan, a political unknown, and Hempstead supervisor Al D'Amato.

[3] D'Amato, who locked up support from Republican leaders on Long Island and had strong ties to the Conservative Party which would ensure his cross-endorsement, was considered a serious threat.

[3] On January 17, former Representative Bruce Caputo announced that he would enter the race for the Conservative and Republican nominations, assuming Javits ran.

Most speculation surrounded Representative Jack Kemp, a leading Conservative Party fundraiser and active supporter of Ronald Reagan's campaign for president.

[3] When he did finally announce his re-election bid on February 25, Javits shocked supporters by revealing had been diagnosed with a form of amyotrophic lateral sclerosis, better known as Lou Gehrig's disease, eighteen months earlier.

[7] On March 22, the Conservative state committee gave their informal endorsement to D'Amato, pledging to formalize the nomination in June.

There was considerable haggling over whether the committee would weight their votes by party support, which D'Amato favored since most of his strength was in the Conservative base of Queens, Nassau, and Suffolk.

Bess Myerson was the early favorite, having the support of Senator Daniel Patrick Moynihan, New York City mayor Ed Koch, and Governor Hugh Carey.

[12] Holtzman rose quickly in the primary, despite her difficulty expressing criticism of Senator Javits, who remained popular with the same liberal Democrats who supported her campaign.

D'Amato, also running on the Conservative line, proceeded to defeat Democratic U.S. Representative Elizabeth Holtzman and Javits, who ran on the Liberal Party ticket.

In the traditionally liberal state of New York, Javits split the Democratic vote with Holtzman, to give D'Amato a close victory.

[23] On October 31, the New York Daily News reported that Javits stated that he would have dropped out if Holtzman had asked him, but he denied it the next day.