Having first appeared together in the 2001 drug smuggling drama Blow, the actress told Access Hollywood that she has spent years waiting for a chance to reunite with Depp.
"I missed working with him through all those years because we had a great experience… when we were shooting Blow," Cruz said.
She continued: "We work really well together… Now that we are friends and we know each other much more, it's so easy! The dynamic is so fluent."
Cruz went on to tease that she and Depp get on so well that they often held up filming by joking with one another.
"Our problem is that we cannot stop laughing," the Spanish star explained. "That can really become a problem sometimes with us… because some days we could not control ourselves. I always say it's a good problem to have because, in the end, that will reflect on the chemistry of [our] characters."
Earlier this week, Cruz noted that having her son Leo with husband Javier Bardem has "changed [her life] forever".
Pirates of the Caribbean: On Stranger Tides opens on May 18 in the UK and on May 20 in the US.
Watch the trailer for Pirates of the Caribbean: On Stranger Tides below: