Mackenzie married Helen Neil (1826–52) in 1845 and with her had three children, with only one girl, Mary, surviving infancy. Helen and he moved to Sarnia, Ontario (known as Canada West) in 1847 and Mary was born in 1848. They were soon joined from Scotland by the rest of Mackenzie's brothers and his mother. He began working as a general contractor, earning a reputation for being a hard-working, honest man, as well as having a working man's view on fiscal policy. Mackenzie helped construct many courthouses and jails across southern Ontario. A number of these still stand today, including the Sandwich Courthouse and Jail now known as the Mackenzie Hall Cultural Centre in Windsor, Ontario, and the Kent County Courthouse and Jail in Chatham, Ontario. He even bid, unsuccessfully, on the construction of the Parliament buildings in Ottawa in 1859. Helen died in 1852, finally succumbing to the effects of excessive doses of mercury-based calomel used to treat a fever while in Kingston. In 1853, he married Jane Sym (1825–93).