The boot of fly-half Adrian Jarvis saw off the visitors after Irish head coach Toby Booth took off the Premiership's leading points scorer Tom Homer during the second half.
Jarvis' two penalties, adding to one and a conversion by Homer plus tries by Bryn Evans and Topsy Ojo, earned the Exiles a two-point victory.
Sale's Nick Macleod kicked four penalties and converted full-back Rob Miller's early try but they ultimately came up just short.
England cap Shontayne Hape failed a late fitness test for Irish so coach Toby Booth promoted Steve Shingler, who has been at the centre of controversy regarding his eligibility for Scotland's Six Nations Championships squad, from the bench.
But it was Sale who got off to the best possible start when Miller was given an inside pass by centre Johnny Leota to find the slightest of gaps for a try with just six minutes gone.
And within moments, it looked as though the Sharks were finding their gear straight away when Irish infringed 38 metres from their own line to give Macleod, who converted Miller's touchdown, a long-range penalty which he successfully landed.
However, the rest of the half was all Irish as they woke up and created some great attacking situations, two of which they turned into points.
Irish's first two tries were simple, neat scores from the breakdown played across the backs to the left corner.
Evans touched the ball down on 13 minutes cross-field movement which saw Jonathan Spratt give the scoring pass to the big Kiwi.
The Exiles then came into their own, although their two-point half-time advantage did not reflect their territorial advantage in the half.
Ojo, who had a good half, dropped a pass from ex-England full-back Delon Armitage but made up for that mistake soon afterwards when Shingler put him over on the left despite the attentions of Sale wing Tom Brady.
Sale could have conceded a third try when Irish pounded their line but a brilliant turnover from skipper Sam Tuitupou prevented the score.
And Sale's nervy half was epitomised when scrum-half Dwayne Peel tried to clear inside his own 22 only for home number eight Alex Gray to charge down, with the ball flying into touch in goal.
Sharks coach Steve Diamond is not one fo mince his words and the Sale changing room may not have been one for the faint-hearted at the break.
As such, Sale responded with some early territory as the pack, with flanker Richie Vernon and number eight Andy Powell to the fore, caused the home side problems.
Irish did themselves no favours either when hooker David Paice was sent to the sin-bin for a dump tackle on Wales number eight Andy Powell.
But, while Macleod put Sale into a one-point lead with the resultant 40-metre penalty, they did not take full advantage of their numerical superiority.
And, as Macleod, Homer and then Jarvis exchanged penalties with the clock ticking down, it was anyone's match as the Londoners led 18-16.
The lead changed again and again as replacement wing Marland Yarde went charging into the visiting midfield unnecessarily, allowing Macleod to kick his fourth penalty for a 19-18 Sale advantage before a scrum error by Sale handed Jarvis his second penalty of the half to seal the match.
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