During his time with the Bank of Montreal, Angus was free to pursue opportunities for private investment. In 1868, he went into partnership with the future Lords Mount Stephen and Strathcona at the time that they were becoming interested in developing railways across to the Canadian West. Their ventures were largely financed by the Bank of Montreal, of which Mount Stephen was President and as his number two at the bank, Angus, was closely involved. Angus resigned from the bank in 1879, briefly relocating to St. Paul, Minnesota to represent the group's interests there as vice-president of the Saint Paul & Pacific Railroad.

In Minnesota, Angus had worked closely with James J. Hill, constructing and improving the line. But by 1880, he spent most of his time with Mount Stephen as they made numerous trips to Ottawa, New York, and London to negotiate the land grants, subsidies, and building of the Canadian Pacific Railway. With Angus providing the analysis and Mount Stephen the acumen, they proved to be a formidable pair. Angus was general manager of the CPR until the appointment of William Cornelius Van Horne in 1882, then Angus became vice-president. In that position, Angus was entrusted with the creation of the eastern network, notably the extension of the Ontario & Quebec Railway and the purchase of the western section of the Quebec Montreal Ottawa & Occidental Railway in 1882.

The construction of the CPR was fraught with financial peril, testing the resilience of the syndicate, Hill resigned in 1883, followed by Angus' close friend Duncan McIntyre the next year. To lobby for funds more successfully, Angus resigned from the St. Paul Railway in 1884. The CPR, completed in 1885, was an immediate financial success, becoming "the world's greatest transportation system". He remained vice-president of the CPR after Lord Mount Stephen resigned from an active role as president in 1888. Apparently never aspiring to the position, Angus supported Stephen's selection of Van Horne as president and, 11 years later, Van Horne's choice of Lord Shaughnessy as his successor. Angus would serve as a director and committee member of the CPR for over 40 years, necessitating frequent trips to the Canadian Pacific Offices at Trafalgar Square in London - Wikipedia.