Zellweger, 50, who won the award for her riveting portrayal of Hollywood legend Judy Garland, crammed her speech full of grateful shoutouts to her fellow nominees and former co-stars, including Cruise "for your example of professionalism on set and striving for excellence and generosity and unconditional kindness."
The two shared the screen in the 1996 rom-com, which rocketed Zellweger to fame. Cruise, 57, played Jerry Maguire, a slick sports agent determined to start his own agency, while Zellweger played Dorothy, a young single mom who shared in his dream.
Fans of the film took to Twitter after Zellweger's nostalgic remark.
"Renee Zellwegger (sic) shouting out Tom Cruise was pretty cool," tweeted one user. "Cruise rarely gets nominated anymore but his work ethic on the set, creates a blueprint for his fellow actors to follow."
Another fan shared a shot of Cruise as Jerry Maguire wearing shades with a grin on his face.
The win is just the latest for Zellweger, who recently returned to acting after a six-year break. She also racked up a Golden Globe Award and a Critics Choice Award for her work in "Judy." Next month, she'll head to the Oscars to compete for her second Academy Award.