D'Ambrosio made his race début for Lotus at the 2012 Italian Grand Prix; he replaced Grosjean, who was banned for one race for causing a multiple collision at the previous round in Belgium. He qualified in 16th place, and started in 15th place due to a 10-place grid drop penalty applied to Pastor Maldonado. He finished in 13th place, on the lead lap, 76 seconds behind.