It's Waltrip's second win at the 500 in the last three years.
The race was supposed to be 200 laps, but two heavy rain showers forced the first shortening of the race since 1966.
Kurt Busch finished second, followed by Jimmie Johnson and Kevin Harvick. Mark Martin, last year's series runner-up, was fifth, with Robby Gordon sixth and defending Winston Cup champion Tony Stewart seventh.
Dale Earnhardt Jr., the pre-race favorite whose father Dale Earnhardt Sr. died at Daytona two years ago in a last-lap crash, finished 36th.
Waltrip's first Daytona win was in 2001, the race in which his friend and teammate, Earnhardt Sr., died.
All three drivers involved in a spectacle of a crash during Sunday's race -- Ken Schrader, Ryan Newman and Bobby Labonte -- have been checked out medically and are OK.
This was the third time in the race's 45 editions that the Daytona 500 was shortened by rain. Fred Lorenzen ran 133 laps in winning in 1965, and Richard Petty took the 1966 race in 198 laps.