The fire broke out around 5:15 p.m. in the 12200 block of Millbanks Drive near Amberwick.
Houston Fire Department said crews responded to a call about a person possibly trapped inside the home.
When firefighters arrived, they found fire in the kitchen and the body of a 68-year-old man inside.
Neighbors said the man lived by himself inside the home and had "a lot of medical problems."
"I broke one of the doors inside, where the master is. I broke it in. I was trying to get inside, but I couldn't. There was too much smoke already. We were all trying to bust out windows and get to him, but it was just too full of smoke already," Ever Guevara, a neighbor, said.
Investigators believed the victim was trying to put out the fire when he died.
The cause of the fire was not immediately known.