The house, located on a hillock at Mharal village in Kalyan tehsil, collapsed at around 2.30 am after the region witnessed heavy downpour for the last two days, district disaster management officer Asmita Nikam said.
As the structure collapsed, the people living inside it and a couple sleeping in an adjacent house got trapped under the debris, she said.
The firemen rushed to the spot and retrieved two bodies from the house.
The deceased were identified as Saifuddin Khan and Aladdin Shaikh (both aged 45), she said.
The four injured persons were admitted to a government hospital in Ulhasnagar, she added.