The win sees London leapfrog Sale into seventh place in the Guinness Premiership.Â
Fly-half Shane Geraghty kicked nine points for the Exiles after Sailosi Tagicakibau's first-half try had given the visitors the impetus from a slow start.
Mark Cueto captained the side from an unfamiliar position of full-back and Sale started the game brightly with scrum-half Richard Wigglesworth causing London problems around the ruck area.
With Daniel Larrechea and England's Charlie Hodgson on the sidelines, fly-half Lee Thomas was given the kicking duties and he stoked the ball between the posts from just inside the Exiles half to give the Sharks the lead after 10 minutes.
Opposite number Geraghty tried his luck from similar range in the 15th minute after Sale had been caught offside. But he pushed his effort wide of the posts.
The hosts continued to dominate and, following an unsuccessful penalty goal attempt, Thomas doubled the lead from the centre of the field.
Irish, who had just one Premiership win in their last five games prior to the match, hit back and scored the first try of the game.
Slick passing from the Exiles backs saw them outnumber the Sharks on the left wing, and Tagicakibau dived into the corner for his fourth try of the season to reduce the scores to 6-5.
Irish missed the opportunity to take the lead when Geraghty's conversion struck the upright but he made amends just two minutes later, sending over a penalty to give the visitors an 8-6 lead at the break.
Geraghty was on top form again after the restart, firing over from 35 metres before a long-range drop goal extended the lead to eight points.
Sheridan's introduction with half an hour to play saw Sale spark into life but a resolute London defence held their line.
And the Sharks' woes increased midway through the half, as second row Dean Schofield was shown his second yellow card of the season after holding onto the ball in a ruck.
Thomas reduced the deficit to earn a losing bonus point with 10 minutes remaining when he converted a simple penalty, but London held on for the much-needed victory.