Prescott made the announcement in a four-page statement on Instagram:
"As our communities take action, protesting and fighting for the justice of George Floyd and every black life, I am with you! I have viewed these protests and riots in our streets as a form of strength and an attempt to show we as black people have rights that aren't perceived equally as our counterparts," wrote Prescott.
He added: "We will clean our streets and our communities, not only of the looting and violence, but, most importantly, (of) the racism, racial profiling, and hate!"
Prescott also called on police to hold their fellow officers accountable.
"To the men and women that police our streets, I have the utmost respect for those of you with a passion for protecting and serving our communities," Prescott wrote. "When you chose to wear a badge of a police officer, you pledged to PROTECT life and property through the enforcement of our laws and regulations.
"How can you claim to uphold the law when those within your ranks don't abide by it? You need to hold your own accountable! Each of you are as guilty as the men who stood beside Derek Chauvin if you do not stand up against the systemic racism plaguing our police forces nationwide."
In the wake of Floyd's death while in the custody of Minnesota police, and subsequent nationwide protests, high-profile quarterbacks such as 2020 No. 1 pick Joe Burrow and Carson Wentz have spoken out against police brutality and racial inequality.
But Prescott is the first to make a seven-figure donation to help combat the crisis.
The Cowboys quarterback is set to earn $31.8 million in 2020 while on the franchise tag. Prescott was among the lowest-paid starters in the league while on his rookie contract, averaging around $1 million a year since being drafted in 2016.