He finished ahead of Bayern Munich's Sadio Mane and Manchester City's Kevin de Bruyne, who came in second and third, respectively. PSG striker Kylian Mbappe came in sixth, while Manchester United forward Cristiano Ronaldo was 20th.
"I'm really proud seeing this prize, it's been my dream since I was a kid. I grew up with this in my head, and after that I had the motivation," Benzema said.
"I had two role models in my life: Zizou [Zinedine Zidane] and [Brazil legend] Ronaldo. It's a lot of work; I never gave up and I kept that dream in my head. Anything is possible.
"It's been difficult for me. There was a time when I wasn't playing for the national team, but I didn't give up. It's been difficult for me and that just makes me stronger mentally. I'm really happy with my work."
The France international picked up the prize -- which is awarded by the magazine France Football -- for the first time in his career at a ceremony at the Theatre du Chatelet in Paris.
He is the first Madrid player to receive the award since Luka Modric in 2018, and the first Frenchman to win since 1998 honoree Zidane, who awarded Benzema the trophy.
"I'd like to thank my teammates at Real Madrid and the national team, my president [Florentino Perez] who is like family to me, and also the Lyon academy and president [Jean Michel] Aulas, thanks to him I fulfilled my dream of playing for Real Madrid," Benzema added.
Lionel Messi won the award in 2019 and 2021, while no Ballon d'Or was given out in 2020 because of the COVID-19 pandemic.
In 13 years at Madrid, Benzema has lifted five Champions League trophies, four LaLiga titles, two Copas del Rey, four UEFA Super Cups and four Spanish Supercopas.
Benzema received widespread recognition for his performances in the Champions League last season, scoring 10 goals in Madrid's knockout stage wins over PSG, Chelsea and Manchester City on the way to winning the club's 14th European Cup.
After a six-year absence from the France national team, he returned to help them win the UEFA Nations League in 2021 and is expected to lead their attack at the 2022 World Cup in Qatar.
Earlier in the ceremony, Barca midfielder Gavi won the Kopa Trophy, the award presented to the best player under age 21.
After breaking into the first-team setup at age 16 last year, Gavi went on to make 47 appearances for Barca in all competitions in 2021-22, scoring two goals.
His performances for the Catalan club earned him a call-up to the Spain national team and he became the youngest player to ever represent La Roja, at the age of 17 years and 62 days.
Gavi has since won 12 caps for Spain and is a regular for club and country heading into next month's World Cup.
Ballon d'Or organisers added a humanitarian prize named after the late Brazil midfielder Socrates. The trophy went to Mane for his charity work in Senegal, including building a hospital and donating to schools.