"Captain America: The Winter Soldier" added another $26 million to its coffers, according to studio estimates Sunday, while Depp's sci-fi thriller, "Transcendence," opened in fourth place with $11 million.
Directed by longtime Christopher Nolan cinematographer Wally Pfister, the Warner Bros. film is Depp's third consecutive box office disappointment. He played Tonto in last summer's "The Lone Ranger" -- one of the biggest flops of 2013 -- and starred in 2012's comedy-horror dud, "Dark Shadows."
"As we approach the summer movie season, box-office drawing power becomes more about the concept of the movie rather than its star," said Paul Dergarabedian, senior media analyst for box-office tracker Rentrak. "It may not have been so much (about) Johnny Depp, but audiences right now like brands that they know."
That doesn't bode well for original ideas, such as "Transcendence," penned by first-time screenwriter Jack Paglen. Dergarabedian notes that 12 sequels are expected this summer alone.
"This is all reality. This is stuff that's going to be real in the next 30 years," Depp told CBS News about the film about establishing a world where computers can transcend the abilities of the human brain.
Another new movie, the religious-themed "Heaven Is for Real," debuted in third place over Easter weekend, starring Greg Kinnear, Thomas Haden Church and Kelly Reilly.
"Rio 2," which features the voice of Jamie Foxx, Kristin Chenoweth and Jesse Eisenberg, held on to the second spot.
"The Winter Soldier" set a box-office record as the biggest April release ever when it opened with more than $96 million domestically. Starring Chris Evans as comic book hero Capt. America and Scarlett Johansson as Black Widow, the Disney release has earned more than $200 million to date in North America -- the 12th Marvel film to do so.