Lookman scored all three goals, ending Leverkusen's extraordinary unbeaten run and earning 66-year-old coach Gian Piero Gasperini the first major trophy of his long career.
The Atalanta earned a series of chances later, but poor finishing let them down. Atalanta's task was made harder after Gosens collected his second yellow card after trampling on Jordan Veretout.
Madrid had reached the semifinals or better in eight straight seasons between 2010-11 and 2017-18 before losing to Ajax in the last 16 in 2019 and to Manchester City last season.
Madrid entered the game as the big favorite despite a slew of injuries, and Atalanta's chances diminished further when midfielder Remo Freuler was sent off.
"Ronaldo carried out a check with a diagnostic test (swab) for Covid-19. The exam provided a negative result," the Italian champions said in a statement.
