Blazer, who has had his own finances probed by the FBI, said in a statement issued by the regional confederation on Thursday that he wanted to "pursue other career opportunities in the burgeoning industry of international football."
The 66-year-old added, however, that he will retain his seat on FIFA's decision-making executive committee, which he has held since 1997.
The American, a close ally of FIFA President Sepp Blatter and one of world football's power brokers, had been at the helm of the regional body representing North and Central America and the Caribbean for 21 years.
"My passion for soccer is undiminished and it is time for me to explore new challenges within this wonderful sport," Blazer said.
"Running a governing body has been an incredibly fulfilling job, but there are so many other areas of the sport where, as a senior executive, I will make a great impact."
Blazer had worked closely with former CONCACAF president, Trinidadian Jack Warner, throughout his time at the confederation but earlier this year he gave evidence to FIFA's Ethics Committee that led to Warner's resignation.
The American provided documentation that led to a lifetime ban for Qatar's Asian Football Confederation chief Mohamed Bin Hammam, who had been challenging Blatter for the FIFA presidency.
In an email to Reuters in August, Blazer did not deny receiving three offshore payments but insisted that "all of my transactions have been conducted legally."
Blazer's reign at CONCACAF has seen the organisation hugely expand its range of competitions and revenue sources with the bi-annual Gold Cup increasingly well attended and drawing large audiences on Spanish language television in North America.
