The measure was approved by a voice vote with no objections on Monday.
Democratic Senator Mary Landrieu, from the southern state of Louisiana, described lynching as “an act of domestic terrorism.”
She said it is an appropriate time to initiate the apology “as our country leads the fight against terrorism abroad.”
Ms Landrieu co-sponsored the measure along with Republican Senator George Allen of Virginia.
The US House of Representatives passed anti-lynching legislation three times between 1920 and 1940, but the measures were not approved by the senate, despite support from seven US presidents between 1890 and 1952.
The bills were knocked down by powerful Southern senators, some of whom argued that such laws interfered with states’ rights.
However others maintained that lynching helped control potential threats of physical abuse to white women and also served to keep the races separate, according to a Washington Post article citing records provided by lobby group Committee for a Formal Apology.
Historians have documented 4,742 lynchings between 1880 and 1960, mostly of black men in the racially segregated southern states, over accusations of minor or non-existent transgressions.
Owning a successful farm or arguing with a white man about cotton prices was worthy of a lynching.
Around 200 descendants of lynching victims were present at the US Capitol to witness the event.
The only known living survivor of an attempted lynching, James Cameron, now 91, was also present for the signing.
Mr Cameron, who is black, was nearly lynched with two black friends when he was 16 years old, however was saved at the last minute when a member of the crowd protested.
“The apology is a good idea, but it still won’t bring anyone back,” he said.
“I hope the next time it won’t take so long to admit our mistakes.”
Meanwhile, a court has started jury selection proceedings for a 41-year-old murder case involving a former Baptist minister accused of killing three young civil rights workers.
Edgar Ray Killen, 80, was brought into court in a wheelchair as police ushered around 110 potential jurors into the county courthouse through a side door, in the town of Philadelphia, Mississippi.
Killen was arrested in January this year and charged with masterminding the murders of Michael Schwerner, 24, Andy Goodman, 20, and James Chaney, 21, in June 1964.
Their deaths were vividly dramatised in the 1988 feature movie Mississippi Burning.
At the time of the slayings, Killen worked as a saw-mill operator and part-time preacher, and is suspected of belonging to the Ku Klux Klan, a white supremacist group spawned in the American south.
Mr Schwerner and Mr Goodman, both white men from New York, had teamed up with Mr Chaney, an African-American Mississippi local, to help black voters register to vote.
They had been detained by police for several hours on June 21 of that year for speeding.
FBI records and witness testimonies allege Killen was responsible for organising carloads of Klansmen to follow the trio after they were released and stopping them in their station-wagon.
The bodies of the three men were found 44 days later, buried under an earth dam.
They had been beaten and shot to death.
Killen was among a group of 18 men tried in 1967 on charges of violating the victims’ civil rights.
Seven men were convicted, but Killen was acquitted by a deadlocked jury.
He is the only person connected with the case to face state murder charges.
Prosecutors in southern US states have re-opened a number of so-called atonement cases in recent years, including a conviction three years ago for the 1963 fire-bombing of a church in Birmingham, Alabama, in which four African-American girls were killed.
Opening arguments in Killen’s trial are expected to begin later this week.