The 49-year-old, who made 41 Grand Prix starts in the Nineties, beat Australia's Stuart Tripp to the gold by just 2.74s, despite being 10s behind at the halfway point of the 20km course.
It was the Italian's third gold and fourth medal overall at the Paralympics - he triumphed in the Men's Individual H4 Time Trial and Road Race at the 2012 London games (pictured) - adding to the six world championship gold medals he has achieved since moving into handcycling in 2007.
Zanardi was competing on the eve of the 15-year anniversary of the terrible Champ Car accident at the Lausitzring that cost him both his legs and very nearly his life.
He will be in action again on Friday, competing as part of a three-man Italian team in the H2-H5 team mixed relay.
Zanardi debuted in F1 with Jordan in 1991 and had a one-off outing with Minardi the following year before spending two years with Lotus. A subsequent move to America yielded the popular racer two Champ Car titles in three years, and helped secure his return to F1 with Williams in 1999.
Remarkably Zanardi returned to racing after his horrific 2001 accident, using hand controls to compete successfully in various touring car and GT racing championships.