Henin won seven Grand Slam singles titles and spent 117 weeks atop the WTA rankings, while Safin collected two major crowns and spent nine weeks atop the ATP rankings.
Set for posthumous induction in July 16 ceremonies at the ATP Hall of Fame Championships are Frenchman Yvon Petra, who died in 1984 at age 68, and England's Margaret Scriven, who died at age 88 in 2001.
Henin, 33, is the first Belgian player inducted into the Hall of Fame. She won 43 career singles titles before retiring in 2011, including the 2004 Australian Open, 2003 and 2007 US Opens and 2003, 2005, 2006 and 2007 French Opens.
"It's a big honour," Henin said.
"I was five years old when I started playing tennis and my dream was to become a champion. All of the things that then happened - all the dreams that came true, all the victories and Grand Slams, and every emotion that I lived in my tennis career - remain something very important in my life."
Safin, 36, is the first Russian player inducted into the Hall of Fame. He won 15 career titles, including the 2000 US Open and 2005 Australian Open, before retiring in 2009.
"I'm very happy to be inducted to the Hall of Fame," Safin said.
"To be part of a Hall of Fame is every athlete's dream. I am really honored to be inducted and proud to represent Russian tennis alongside the greatest champions of tennis history."
Petra won the Wimbledon men's singles title in 1946, after spending five years as a prisoner of war in Germany, according to the Hall of Fame.
He is the most recent French winner of the men's Wimbledon singles crown.
Scriven won the French title in 1933 and 1934, becoming the first left-handed woman to capture a Grand Slam crown and the only unseeded winner of the French championships.
"Their success is part of the sport's storied history and we're glad to recognize their accomplishments," said Hall of Fame president Stan Smith.