Information about 14-year-old Emmett Till, who was murdered during a family holiday to Mississippi, was scraped and later peeled off a historical marker.
The murder of the Chicago teenager made headlines throughout the US when photos of his body were published in 1955.
Another Till memorial nearby was found riddled with bullet holes in 2016.
The latest vandalism happened to a marker placed outside the Bryant Grocery store in Money, Mississippi, where the teenager was accused of whistling at a white woman. It was also defaced in May.
Allan Hammons, whose company manages the Mississippi Freedom Trail where the sign is located, says he does not know if the new vandalism is racially motivated, but adds that it was the only sign on the trail that was defaced.
Davis Houck, a member of the Emmett Till Memory Project, told the Clarion-Ledger: "This time, it's not someone with a shotgun or somebody trying to run over or tear down the sign."
"This time, it's more sinister because it's carefully thought out. It's not a defacing, but an erasing."
The monument, which was erected by the Mississippi state tourism board in 2011, will cost around $500 (£400) to repair, officials say.
Visiting students from St Louis-based social justice group Cultural Leadership, who discovered the vandalism on Sunday, replaced the missing text with their own accounts of Emmett's life and death.
Two white men were arrested for the brutal crime, but acquitted by an all-white jury later that year.
The decision by his mother, Mamie Till Mobley, to allow photos of his open coffin to be published after his return to Chicago drew tens of thousands of mostly African-American mourners.
A memorial to an African-American boy whose lynching galvanised the US civil rights movement has been vandalised for the second time in as many months.