Meanwhile, with Wellington's centre exposed by the fall of La Haye Sainte and the Plancenoit front temporarily stabilised, Napoleon committed his last reserve, the hitherto-undefeated Imperial Guard infantry. This attack, mounted at around 19:30, was intended to break through Wellington's centre and roll up his line away from the Prussians.

Other troops rallied to support the advance of the Guard. On the left infantry from Reille's corps that was not engaged with Hougoumont and cavalry advanced. On the right all the now rallied elements of D'Érlon's corps once again ascended the ridge and engaged the Anglo-allied line. Of these, Pégot's brigade broke into skirmish order and moved north and west of La Haye Sainte and provided fire support to Ney, once again unhorsed, and Friant's 1st/3rd Grenadiers. The Guards first received fire from some Brunswick battalions, but the return fire of the grenadiers forced them to retire. Next, Colin Halkett's brigade front line consisting of the 30th Foot and 73rd traded fire but they were driven back in confusion into the 33rd and 69th regiments, Halket was shot in the face and seriously wounded and the whole brigade retreated in a mob. Other Anglo-allied troops began to give way as well. A counterattack by the Nassauers and the remains of Kielmansegge's brigade from the Anglo-allied second line, led by the Prince of Orange, was also thrown back and the Prince of Orange was seriously wounded. General Harlet brought up the 4th Grenadiers and the Anglo-allied centre was now in serious danger of breaking.

It was at this critical moment that the Dutch General Chassé engaged the advancing French forces. Chassé's relatively fresh Dutch division was sent against them, led by a battery of Dutch horse-artillery commanded by Captain Krahmer de Bichin. The battery opened a destructive fire into the 1st/3rd Grenadiers' flank. This still did not stop the Guard's advance, so Chassé ordered his first brigade, commanded by Colonel Hendrik Detmers, to charge the outnumbered French with the bayonet; the French grenadiers then faltered and broke. The 4th Grenadiers, seeing their comrades retreat and having suffered heavy casualties themselves, now wheeled right about and retired.