The race featured 32,118 runners and was won by Ruben Garcia, a corporal in the Mexican Navy, and Laura Thompson, of Boise, Idaho.
The man who died collapsed before reaching the 17-mile mark near the 14th Street Bridge and was airlifted by helicopter to Washington Hospital Center, race spokesman Beth Cline said.
It appears he had a heart attack, District of Columbia Police spokesman Sgt. Joe Gentile said. Race director Rick Nealis said officials were trying to locate the next of kin.
Nealis said another runner had a heart attack about 80 yards from the starting line. He was revived and thought to be in stable condition in a hospital, he added.
Garcia won for the second straight year, finishing in 2 hours, 21 minutes, 17 seconds and more than three minutes ahead of his nearest rival. He lives and trains in Mexico City but lists Washington as his hometown for "The People's Marathon."
Garcia took the lead from Kenya's Jared Nyamboki during the 22nd mile and coasted to victory. Carl Rundell, of Birmingham, Mich., finished second, covering the 26.2 miles in 2:24:22. Jose Miranda, of Washington, was third in 2:26:21.
The 35-year-old Garcia is the second back-to-back winner among the men, following Jim Haage, of Lanham, Md., in 1998 and 1999.
Thompson was timed in 3:00:10. Brenda Schrank was the women's runner-up in 3:02:28 and Suzanne Himes was third.