Desisa finished in an unofficial two hours, 10 minutes and 23 seconds, besting Ethiopia's Gebregziabher Gebremariam and Kenya's Micah Kogo in a finishing sprint.
Jeptoo closed up in an unofficial two hours, 26 minutes and 25 seconds, crossing the finish line more than 30 seconds ahead of her nearest challenger, Meseret Hailu of Ethiopia.
Americans took fourth place in both races, with Jason Hartmann and Shalane Flanagan finishing just off the podium. No American has won since Lisa Larsen-Weidenbach in 1985.
Jeptoo passed Portugal's Ana Dulce Felix, who had held a commanding lead for eight miles, in the 24th mile of the 117th running of the race.
Runners faced milder conditions on Monday than they had a year earlier, with the temperature in Boston reaching 54 degrees Fahrenheit (12C) at the finish, well below the 84 degrees Fahrenheit (29C) in 2012.
(For more sports news and updates, follow Ahram Online Sports on Twitter at @AO Sports and on Facebook at AhramOnlineSports)