The first lady called the Long Island congressman "a follower, not a leader" and accused him of voting "against the interests of New York women, children and families" because of his positions opposing gun licensing, a patient's bill of rights and federal funding for abortions for poor women.
Lazio's spokesman Dan McLagan fired back, saying: "Mrs. Clinton's campaign is out of state, out of touch, out of ideas and maybe even a little bit out of control."
Lazio, in Washington, said he was "disappointed" by Clinton's "mudslinging."
The laundry list of criticisms from Clinton was a dramatic departure from her usual campaign style. When she faced Mayor Rudolph Giuliani as the Senate candidate, she made the occasional snide remark about his belligerent personality and sometimes critiqued city policies, but usually left sustained attacks to her staff.
But on Wednesday she went on the offensive against Lazio and kept it up throughout a half-hour speech to 1,100 supporters attending a "New York Women for Hillary" breakfast fund-raiser at the Waldorf-Astoria.
On abortion, Clinton pledged to use Roe v. Wade as a litmus test in confirming Supreme Court nominees and noted that Lazio has voted against federal funding for abortions for poor women.
"My opponent calls himself pro-choice, but if you look at his record, he's apparently pro-choice for rich women," she said.
On gun control, Clinton said she would work for mandatory nationwide licensing and registration of handguns, which is already the law in New York state but is opposed by Lazio.
"My opponent has called licensing extreme," Clinton said. "I don't understand that. He lives in a district that has tough gun measures that include licensing and registration. But apparently he is willing to go along with the Republican leadership and the NRA rather than the children and families of New York."
Lazio responded:"I am really disappointed about the direction and tone she's set for her campaign. If this was really about serving the people of New York, this is not the kind of campaign she should wage. I understand her frustration about not really being able to maybe connect with the voters of New York, but I just think New Yorkers deserve better than this kind of mudslinging and I hope we can return to the issues."
Rick Wilson, a Republican political consultant who worked on Giuliani's now-defunct Senate campaign, called Clinton's attack "an interesting departure" from her usual "staying above the fray and seeming more of a statesman."
Wilson said the change "indicates she's a little nervous" because of polls that show Lazio running nearly even with her. "She wants to bring home Dmocrats by ratcheting up the ideological language," he said.
Pollster Mickey Blum of Blum & Weprin said polls show voters are actually closer to Clinton's positions on many issues than Lazio's, "so it behooves her to talk about the difference."