Andrew Demetriou will officially end his 11-year tenure as CEO on June 5, but AFL chairman Mike Fitzpatrick said McLachlan was now effectively the chief.
Demetriou's final event as CEO will be the annual AFL Hall of Fame function on June 4.
McLachlan told a media conference at AFL House that he was "incredibly proud" to have been appointed as chief executive.
"I understand the honour, I understand the responsibility, I understand the privilege of leading this code and this game."
He said he would be "a different leader, with a different approach" to Demetriou, and the shape and structure of the AFL would change.
McLachlan said his understanding of the ongoing ASADA investigation inro Essendon's supplements program in 2012 was that any infraction notices against players would be issued in the second half of May.
Among the most pressing challenges he said he faced were supporting the weaker clubs, and engaging with fans.
He also said he personally preferred a daytime Grand Final.
Fitzpatrick said, "It is very rewarding to be able to appoint from our own game the highest quality and standout candidate for this position. It is testament to Gill and the quality he brings, and testament to our industry’s capacity to develop and plan for our game’s future.
"Gill clearly has the experience and knowledge to lead the AFL.
"But he also put to the AFL Commission a compelling and detailed view of the challenges and issues for the future of our game, and his plan for these challenges."
McLachlan told the media conference, "I want to congratulate Andrew Demetriou on his success and thank him for his support. He leaves incredibly big shoes to fill. He leaves a massive legacy which I hope to build on.
"We have an amazing game, played by the most extraordinary athletes, with the most tribal of clubs and the most passionate of fans. We have our challenges but we are in an amazingly strong position and I am incredibly excited about our future."
Deputy CEO McLachlan, 40, had been the frontrunner to take up the post since Demetriou announced in early March he would be standing down.
McLachlan, who joined the AFL in 2000, has been groomed as Demetriou's replacement and received widespread backing from clubs once the AFL started its search for a new CEO.
It has been reported that club chiefs Brendon Gale (Richmond), Brian Cook (Geelong), Stuart Fox (Hawthorn), Gary Pert (Collingwood) and David Matthews (Greater Western Sydney) were approached as part of a two-month search for Demetriou's replacement.
Fitzpatrick said the executive search identified up to 100 candidates, which was narrowed to 20 and finally to three, who were interviewed on Monday.
Demetriou had initially intended to stand down at the end of the 2014 season, but he will now make way for McLachlan in June.
The 53-year-old, who took over from Wayne Jackson as League CEO in 2003, did not play a role in the appointment of his successor.
McLachlan joined the AFL as a strategic planner and was appointed general manager of commercial operation in 2003.
The South Australian was promoted to the position of chief operating office in 2008, playing a key role in broadcast and digital media, fixturing, venue agreements and stadia infrastructure.
He was acting CEO for a two-month period in 2012 when Demetriou went on long service leave.
Collingwood president Eddie McGuire labelled McLachlan "the No.1 seed without any doubt" following Demetriou's announcement and said it would take "someone pretty spectacular" to beat him to the appointment.
Club support for McLachlan also came from North Melbourne chairman James Brayshaw, who called on the AFL to appoint him immediately in early March.
"I think he's outstanding … and he's got great respect at club land, certainly at our footy club," Brayshaw said.
McLachlan will also sit on the AFL Commission and said he did not expect to appoint a deputy as CEO.
