The win put Monaco, who face Juventus in the first leg of their Champions League semi-final on Wednesday, top with 83 points from 34 games, three ahead of Paris Saint-Germain in second and nine ahead of third-placed Nice.
Toulouse striker Ola Toivonen gave his side a shock lead just after the break, jolting the 18-year-old Mbappe into life as he created a slew of chances for his side in the second half.
Monaco defender Kamil Glik headed home a cleverly-worked corner to equalise before Mbappe added a superb second goal, smashing a low, first-time shot in at the near post, and he went on to torment the Toulouse defence before being substituted late on.
Winger Thomas Lemar netted his eighth league goal of the season to put his side 3-1 up, half-volleying home Nabil Dirar's beautiful, chipped cross 15 minutes from time, and Monaco had plenty of chances to increase their lead even further.
PSG, who thrashed a second-string Monaco side 5-0 in the French Cup in the week, travel to Nice on Sunday.
(Reporting by Philip O'Connor; Editing by Clare Fallon)
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