Smith previously held the role with Exiles for three years between 2005 and 2008, taking the club to third place in the Premiership, the final of the European Challenge Cup and a Heineken Cup semi-final against Toulouse.
He will now work alongside head coach Toby Booth as the club look to halt a four-match losing streak with a win against Leicester Tigers in the St Patricks Day clash on March 25.
Smith, who left Exiles in 2008 to join England, has signed a deal until the end of the 2014-15 season.
He said: "I am delighted to be returning to London Irish. Toby and I have always had a great relationship and that brought with it a lot of success on field in my time at the club and I know that we're destined for even greater things.
Smith, who played for Australia and Ireland, left his role as England attack coach following the 2011 World Cup after he came under fire in leaked reports from the players' union.
But he believes that despite Exiles' recent struggles, the future is bright at the club.
" We're building a new squad with fantastic potential and if we all pull together we can really make things happen," he commented.
Andy Martin, London Irish CEO, added: "We have made great strides over the past couple of years to make this club successful both on and off the field by building a team which has a good mix of experience and raw talent. We are delighted therefore that Brian will be returning.
"He is a top class manager with a proven track record of success both at club and international level. We believe that his experience will help to strengthen our current resources and will be the boost we need to get back on track this season and beyond.
"There is no doubt that it has been a tough few weeks, something that we are all feeling. We would like to thank our supporters most sincerely for sticking with us and hope they will see that we are committed to making positive changes towards future success."