James spoke about the incident, which is being investigated as a possible hate crime, in a press conference scheduled for the opening of the NBA Finals.
"No matter how much money you have, no matter how famous you are, no matter how many people admire you, being black in America is tough," he said.
"We got a long way to go for us as a society and for us as African Americans until we feel equal in America."
A racist slur was spray-painted on the front gate of James' Los Angeles home, LA police told CNN.
Police received a call Wednesday morning but by the time officers had arrived management staff had painted over the offending word, LA Police Department officer Aareon Jefferson said.
The Cleveland Cavaliers star bought the house just over two years ago for just under $21 million, according to public records.
The small forward, who leads the defending champions into the opening game of the NBA Finals Thursday night, was not at home.
During the press conference, James expressed relief that his family was unharmed. "My family is safe and that's what's important," he said.
Game 1 of the series against the Golden State Warriors takes place in Oakland, California.
His statement Wednesday is not the first time that the 33-year-old NBA superstar has been candid about race.
Last year, James and fellow NBA players Dwyane Wade, Chris Paul, and Carmelo Anthony spoke to the issue at the ESPY awards
"Tonight we're honoring Muhammad Ali, the GOAT," James said. "But to do his legacy any justice, let's use this moment as a call to action to all professional athletes to educate ourselves, explore these issues, speak up, use our influence and renounce all violence and, most importantly, go back to our communities, invest our time, our resources, help rebuild them, help strengthen them, help change them.
"We all have to do better."
Last year, ahead of the opening of the 2016-17 NBA season, James, one of the league's most successful players ever, also voiced his concerns
about his children growing up in a country in which black deaths at the hands of law enforcement officers are a very visible issue.
"I look at my son being four years removed from driving his own car and being able to leave the house on his own," James said.
"And you see these videos that continue to come out. It's a scary-ass situation that if my son calls me and said he's been pulled over, that I'm not that confident that things are going to go well and that my son is going to return home."
Police are still investigating the graffiti incident and are examining security camera footage in an attempt to identify the perpetrator. Jefferson, the LAPD officer, told CNN that they cannot currently say if the home was burgled.