On September 9, 1961, in the chapel at Frederiksborg Castle in Hillerød, Denmark, Ambassador Blair married Catherine "Deeda" Gerlach (born 1931), the former wife of oleomargarine heir Charles Clarke Jelke and the only daughter of Norman Harbridge Gerlach (1904–1980), a partner in the Chicago law firm Gerlach & O'Brien, and his wife, the former Joanna Powell. Deeda Blair (who was later a subject of portraits by Andy Warhol)[4] was named director and vice-president of the Lasker Foundation in 1965 and is a noted advocate for public health issues.
The couple had one child, a son named William McCormick Blair III, who committed suicide in May 2004 at age 41. After their son's death, they relocated from Washington, D.C., to New York City.[5] He died on August 29, 2015, at his home in Manhattan at the age of 98.[3]