Forlan hit a scrappy winner in only the ninth minute on Thursday night - but the tie is far from over and even without an away goal, Rafael Benitez's side will be optimistic of overturning the result at Anfield next week.
The Reds missed their injured striker Fernando Torres almost as much as the former darling of the Vicente Calderon missed the chance to face his old club, having also been denied that opportunity in the Champions League last season because of more fitness problems.
Benitez had insisted the 1,200-mile journey by coach, train and eventually plane - after UEFA's insistence the match go ahead despite the volcanic ash cloud which grounded flights across Europe - had brought his squad closer together.
If only his defence had been tighter-knit in the ninth minute then they may not have conceded.
No one will ever really know whether their exertions in getting to the Spanish capital had an effect but it was a sloppy piece of marking which cost them.
Forlan became something of a cult hero among United fans with both goals in a 2-1 victory at Anfield in 2002, albeit assisted, it has to be said, by Reds goalkeeper Jerzy Dudek.
And it was he who returned to haunt the Merseysiders when Jose Manuel Jurado's cross from the left dropped over Jamie Carragher and picked him out on the edge of the six-yard area.
His first attempt at a header was reminiscent of those early United days when he earned the nickname "Diego Forlorn" because of his difficulty in scoring.
However, the Uruguayan is a better, more experienced - and even luckier - player now and as ball from his duffed header dropped right at his feet he poked it home off goalkeeper Jose Reina.
Had Yossi Benayoun enjoyed a similar slice of good fortune a minute later from Dirk Kuyt's cross his header would have nestled in the net instead of flying wide of the far post.
The Israeli beat Atletico goalkeeper David de Dea eight minutes later but again the luck was against him, this time by virtue of a wrong offside decision.
Kuyt's mis-hit shot bobbled into the penalty area where Benayoun slotted the ball home only to be denied by an erroneous flag, as television replays proved.
Still Liverpool came forward and Steven Gerrard should have done better moments later when Lucas Leiva put him through only for the captain to shoot left-footed into the side-netting when he should have least hit the target.
But Atletico's threat had not diminished and their neat triangles in the final third of the pitch often cut open the visitors' defence.
Even right-back Tomas Ujfalusi got in on the act, weaving into the penalty area before shooting into the side-netting five minutes before half-time.
Forlan fluffed another a good chance soon after the break when he was put through on the edge of the penalty area but it was Reina's brilliance in producing a one-handed save which denied one-time Liverpool target Simao from Ujfalusi's cross.
The goalkeeper came to his side's rescue again as he beat away Ujfalusi's long-range strike and Carragher cleared as Atletico regained the initiative.
But Liverpool's experience and proud history, this match seeing them become the first English club to play in 16 European semi-finals, ensured they made a fight of it and, more importantly, did not concede again.
Of those 16 last-four encounters they have lost only four overall and their record when playing semi-final second legs at home is seven victories and one draw.
That statistic alone shows the power of Anfield on European nights.
Time will only tell how much Liverpool's long-distance travails on train, coach and plane cost them.
But, with fourth place in the Premier League looking beyond them, anything other than victory next week is likely to bring their season to a premature end.