Settling in Canada West in the growing city of Toronto, Nisbet studied at the newly established Knox College.

His father and siblings also joined him in Oakville, where his four children (all born in Western Canada) resided, after their parents' death in 1874, although two daughters were living with an aunt there from 1870.

After stressing the need for further ministry and mission to the Cree and Metis in Western Canada, the Synod then appointed him to move from Kildonan, further into the North-West.

[4] In 1866, he led a party of pioneers that included his wife, (1864) Mary MacBeth, the daughter of one of the Kildonan Church Elders and member of the Council of Assiniboia, to the Prince Albert area of Rupert's Land (later North-West Territories and now Saskatchewan.)

Two other Red River pioneers assisted him: John McKay and George Flett (related or connected by marriage to Mary MacBeth Nisbet).

Nisbet also continued missionary travels in the North West, and reached as far away as Edmonton, Alberta, as well as making trips back to Oakville, and to important Presbyterian Church meetings.

After living in Prince Albert for almost eight years, Nisbet was forced back east to Kildonan due to ill health, initially with his wife.

The present St. Paul's Presbyterian Church was built on that site in 1906 and was a continuation of the pioneer congregation sprouting from Nisbet's missionary service.