Scott Overall, who is the only British man selected for the Olympics after finishing fifth in Berlin last year, was acting as a pacemaker for his compatriots but pulled out after 15 kilometres with a minor hamstring strain.
Kipsang's dogged performance saw him finish more than two minutes clear of fellow countryman Martin Lel, who finished second and 2010 winner Tsegaye Kebede.
Keitany set a relentless pace to pull away from compatriot Edna Kiplagat in the final three miles and win by more than a minute, with Priscah Jeptoo coming in third.
Kenya's Wilson Kipsang runs on his way to winning the men's London Marathon April 22, 2012. (Photo:Reuters)
She is thought to have set a new personal best and a new Kenyan record on the way to defending her crown.
Approximately 36,000 runners took part in the event.