The Cessna 310 went down just before 4 p.m. about a block from Compton/Woodley Airport, said Federal Aviation Administration spokesman Ian Gregor.
The plane's fuselage crashed through one roof, and its left wing lodged in a second home.
The plane was carrying two men. Both are reported in critical condition.
In one house, a woman was critically injured and a man suffered less serious injuries. In the other home, a woman complained of chest pains.
The crash did not cause a fire, according to Downey fire Capt. Lonnie Kroom.
The flight originated at Montgomery Field in San Diego and was heading for Hawthorne Municipal Airport, about 10 miles away.
The Cessna is owned by Eureka International of Carson City, Nev., Gregor said.
Hawthorne Airport has an air traffic control tower, but it wasn't clear whether the pilot was in contact with controllers.