Lidl-Trek’s Longo Borghini, 32, became only the fifth rider to win a second Women’s Tour of Flanders, adding to her 2015 title.
She edged Poland’s Kasia Niewiadoma into second place in a sprint finish, while the Netherlands’ Shirin van Anrooij was third.
Longo Borghini and Niewiadoma bridged the gap to breakaway leader Van Anrooij with 12km to go and held off the chasing pack.
Three-time world champion Marianne Vos, who won the race in 2013, was fourth – nine seconds back.
“Winning this race means a lot to me,” said Longo Borghini.
“This win is also for Lizzie. Hopefully we put a smile on her face.”
Deignan, 35, was forced to pull out of the race with 145km remaining after being involved in a heavy crash involving 10 riders, including world champion Lotte Kopecky.
Kopecky was able to continue, eventually finishing fifth, but the British rider was taken to hospital for checks, with her Lidl-Trek team confirming an X-ray showed a “fracture of the radial head of the right arm”.