James made a game-winning put-back with 12.8 seconds remaining and played strong defense to force Paul George into missing a three-point attempt at the buzzer that would have secured a win for the Clippers.
James finished the game with 16 points, 11 rebounds and seven assists to earn the Lakers a 103-101 win as the NBA season resumed in dramatic fashion.
Every person present at the game knelt during the national anthem and the players wore warm-up gear showing their support for Black Lives Matter.
Speaking on court after the Lakers victory, James was asked if the showpiece game represented something bigger than basketball.
"Absolutely. The game of basketball has always been bigger than just the ball, the rim, 10 guys on the floor with referees," he said.
"It is an opportunity to use this platform to spread a lot of positives, a lot of love, through the course of the whole world. We understand what is going on in society right now and we are using this NBA platform - as players, coaches and organisations - to continue to stand strong on that.
"This is a good start tonight. It is great to have the NBA back and I hope the fans are proud of us tonight."
James acknowledged progress had been made in the global fight against social injustice, sparked by the killing of George Floyd at the hands of police officers in Minneapolis in May.
"There has been progress. But in the past, when we have seen progress, we have let our foot off the gas a little bit. We can't do that," James said. "We want to continue to keep our foot on the gas, continue to push forward and spread love throughout America.
"We are dealing with a lot of racism, social injustice and police brutality, not only in my neighbourhoods, not only with black people, but with people of colour and it's something we want to continue to have peoples' ears open to. We have [their] ears now, but we cannot stop. [We must] keep our foot on the gas as we have been doing over the last few months."
Reflecting on the Lakers' fourth and final regular season match-up against the Clippers, their chief rivals for supremacy in the Western Conference, James described his game-winning play and revealed a change of footwear mid-game has helped him raise his level of play.
"PG (Paul George) and Kawhi (Leonard) are two superstars in our league and they showed up big time in the absence of Lou Williams and Montrezl (Harrell). We knew they were going to get the bulk of the [Clippers] shots," he said.
"On that last possession, I was able to get a switch and I felt like I got some contact going to the hole but the whistle wasn't called. When you don't hear the whistle you keep playing so I was able to follow my shot up and win the game for us.
"I struggled a lot in the first half. Actually I struggled in the first three quarters getting my rhythm, which is going to come. Switching sneakers definitely put me in a mindset to try to close the game out in the fourth [quarter]."