The veteran striker will bring the curtain down on his loan stay from Helsingborgs after Saturday's FA Cup trip to Middlesbrough, but his 72nd minute header settled a nervy performance by United, who won the tie 2-0 on aggregate following Ryan Giggs' controversial strike two weeks ago in France.
Sir Alex Ferguson opted to name a defensive-looking line-up with John O'Shea preferred to the rested Giggs and the home side, although enjoying plenty of possession, were often on the back foot as Lille searched for a vital away goal.
O'Shea could have handed United a 15th-minute lead but a header from a Michael Carrick corner crashed against the crossbar.
That miss appeared to spur on Lille who looked dangerous particularly when Ludovic Obraniak was allowed to deliver some pinpoint free-kicks.
Jean Makoun missed a gilt-edged chance after 23 minutes when he failed to make a firm contact with a free-kick delivered from a central position and his weak header from six yards was claimed by Edwin Van der Sar.
Peter Odemwingie then hit the upright straight after half-time as Obraniak's free-kick rebounded to him on the back post and he prodded a header past Van der Sar but on to the upright.
Stephane Dumont stung the palms of the United keeper from distance on the hour-mark as Lille continued to look the better side in the final third.
But it was United that broke the deadlock with their one move of real quality on the night 18 minutes from time.
Cristiano Ronaldo outstripped Matthieu Chalme down the right wing with a determined run and clipped over a cross from the byline which Larsson glanced beyond the keeper with a quality header.
Two minutes later, Larsson was replaced by Alan Smith to a standing ovation with the veteran striker pausing for a moment to enjoy the applause ringing around Old Trafford before taking his seat in the dug-out.
United then played out time comfortably but suffered a worrying injury blow in stoppage time when Mikael Silvestre was stretched off after falling awkwardly following an aerial collision with Efstathios Tavlaridis.
The French full-back required five minutes of treatment from a team of medics and appeared to be struggling with head and shoulder injuries as he was carried off the pitch.