Weeks of expected hearings, which coincide with the state election in late November, will investigate the involvement of organised crime and the construction union's alleged grip on worksites.
In opening Monday's hearing, counsel assisting Chris Young KC said several submissions received by the commission appeared "on their face" to be untrue and some disclosed conduct that appeared to be misconduct, corruption, or crime.
November's sessions will examine events at Sunbury's Gap Road project, which involved the removal of a level crossing and the construction of a new rail bridge and underpass.
The Sunbury project was delivered by the Rail Infrastructure Alliance, with the commission to focus on the rail occupation in June 2022.
Under the alliance, industrial relations responsibilities were shared between participants which included the state government, as the project's owner.
In particular, the inquiry will examine events during that month, including a meeting at the CFMEU's offices after a two-day stoppage.
Commissioner Chris Kourakis KC said the arrangements made at that meeting, what they cost and who paid for them would be the subject of inquiry.
"We will examine how much the state knew and what it didn't, and what it did and didn't do about circumstances unfolding there," he said.
Mr Young outlined seven themes which would be the focus of the commission, including CFMEU's influence on worksites and the use of safety and entry powers on sites as industrial leverage.
"It is said that rights given to protect the safety of workers and rights of entry were used to stop critical works and to secure demands," he said.
Another of the commission's themes was what the state did in response to reports of alleged unlawful or corrupt conduct by contractors, with some saying they received no response to years of formal notices.
How contractors left to themselves to manage industrial relations disputes did so, was another of the commission's themes.
"Some say they paid claims they had disputed to end disruption on site," Mr Young said.
"Others say they replaced sub contractors and paid significantly more … because the CFMEU demanded it."
As of Friday the Commission has issued more than 200 notices, resulting in the production of more than 110,000 documents.
Evidence received by the commission so far suggested apparently legitimate businesses paid large amounts to people associated with organised crime, Mr Young said.
"The services they paid for appear to involve little more than intimidation and menace," Mr Young said.
Mr Young described it as "no small task" to rid the construction industry of its alleged links to organised crime.
Premier Ben Carroll vowed to set up the $50 million royal commission as his first act in government after he toppled predecessor Jacinta Allan, who had for months rejected widespread calls to launch a probe.
Ms Allan and her predecessor Daniel Andrews had legal counsel representing them at the commission on Monday, with both open to being called to give evidence.
The commission's final report is due in August 2027.