Del Potro, the No. 2 seed, outfought Dudi Sela of Israel 6-0, 5-7, 6-2, extending his winning streak to 16 matches. He has won three straight tournaments.
American John Isner, runner-up in the Legg Mason event last year, also advanced, eliminating countryman Donald Young 6-4, 7-6 (7-4).
Other second-round winners included Colombian Alejandro Falla and German Tommy Haas.
Notable deaths of 2014 [PHOTOS]
Michael Sam cut from the Dallas Cowboys