The 65-31 vote passed a bill that supporters said protects the industry from financial disaster and bankruptcy caused by damage lawsuits.
"This bill says go after the criminal, don't go after the law-abiding gun manufacturer or the law-abiding gun seller," said bill sponsor Sen. Larry Craig, R-Idaho.
But Sen. Edward Kennedy, D-Mass., and other opponents said the gun industry needs no such special protection. "This bill has one motivation — payback by the Bush administration and the Republican leadership of the Congress to the powerful special interest of the National Rifle Association," he said.
Senate Majority Leader Bill Frist, R-Tenn., yanked similar legislation from debate last year when Democrats successfully attached an extension of the ban on assault-style weapons and the NRA dropped its support.
CBS News Correspondent Bob Fuss reports that while this kind of blanket lawsuit protection sought by the NRA for years has passed the House before, this is the first time the Senate, with its increased republican majority, has passed it.
Republicans picked up four more Senate seats in last November's election, emboldening gun rights supporters to try again.
The House passed a similar bill last year but has taken no action on it this year.
Democrats won inclusion this year of a new requirement that each handgun be sold with a separate child safety or locking device, unless purchased by government officials or police officers. Any violation could be punished by the suspension of a dealer's license, a $10,000 fine, or both.
Craig said the bill does not block gunmakers and dealers from facing product liability, negligence or breach of contract suits.
Its opponents, however, say the bill effectively exempts gun manufacturers from liability. They also say dealers sometimes let weapons get into the hands of people the law says shouldn't have them.
Lawsuits against gun makers and gun stores by victims of gun violence aren't often successful, reports Fuss, but this bill overrides state laws to prevent any from being pursued.
Democrats tried and lost attempts to insert special provisions in the legislation that would let children and police retain the right to sue, along with another amendment that would have let individuals but not municipalities retain the right to sue.
"Should those whose actions lead to the death or injury of a child get a free pass?" asked Sen. Frank Lautenberg, D-N.J., who sponsored one amendment.
Supporters of the liability bill said the changes would have gutted the bill.
The Senate also brushed aside a Kennedy amendment that would have banned hollow-tipped, so-called "cop killer" bullets.
The gun industry gave 88 percent of its campaign contributions, or $1.2 million, to Republicans in the 2004 election cycle. Gun control advocates, meanwhile, gave 98 percent of their contributions, or $93,700, to Democrats during that election, according to the Center for Responsive Politics.