James Riley Blake was born in December 28, 1979 at Yonkers , New York to parents Tom Sr. and Betty. He has a brother, Tom Jr., and two older half-brothers, Christopher and Howard.

At age 13, was diagnosed with severe scoliosis (curvature of spine), which forced him to wear a back brace 18 hours a day.

Blake attended Fairfield Warde High School, in Fairfield, Connecticut. He dropped out of Harvard University after his sophomore year to pursue a career in tennis. Blake was inspired to pursue tennis after hearing his role model, Arthur Ashe, speak to the Harlem Junior Tennis Program. Brian Barker was his first (and current) coach.

At age 21, he saw his first Davis Cup action in 2001 against India, and became the third African-American man to play the Davis Cup for the United States. Blake won the 2002 USTA Waikola Challenger in Hawaii. He has also twice won the Hopman Cup (with Serena Williams & Lindsay Davenport).

At the 2004 Olympic Games in Athens, James played on the U.S. team.

2004 was an especially difficult year for Blake. He broke his neck while practicing at a tournament in Rome in May, developed shingles, and in July lost his father to cancer. James did not know if he would ever play tennis again. However, he persevered with help from his family and friends, reentered the tennis world at No. 210 and climbed up to 49 in the rankings. He entered the 2005 US Open as a wildcard, where he staged a remarkable comeback, defeating 2nd seed Rafael Nadal in the round of 32.

Blake was named Rookie of the Year for the 2000 World Team Tennis season, and he has appeared in the People magazine's Sexiest Man Alive issue. Away from tennis, Blake also likes playing golf, basketball and baseball.