Manzelmann put pen to paper after winning the title with Newcastle last year and taking the QRLW Gold Stars to premiership glory before that.
Born and bred in Mackay, Manzelmann was a member of the Queensland U18s and the inaugural Cowboys Women's Academy.
Manzelmann told a packed media scrum on Tuesday it was an honour to sign with the club after coming through their pathways.
"Growing up there was not much women's footy," she said.
"Then you had all these pathways which I've been through and when the Cowboys said they were putting in a team it was sort of a dream.
"Now that dream's come true."
Manzelmann is the first domino to fall in an expected flurry of signings to be announced in the coming days, four years after North Queensland began plotting to enter a team in the NRLW.
Cowboys CEO Jeff Reibel said it was a monumental day for both the club and rugby league in north Queensland.
"For Emma now to be able to compete on the national stage and do so from a home region is special and why we put this club in place," Reibel said.
The Cowboys confirmed negotiations were also held with Townsville local and fellow 2022 NRLW premiership-winner Romy Teitzel, but the 24-year-old signed with rivals Brisbane this week.
Reibel added the Cowboys were "comfortable" with their position from a recruitment standpoint.
Meanwhile, Gold Coast have signed Australia playmaker Taliah Fuimaono on a three-year deal as she became the club's sixth new signing ahead of the 2023 season.
Fuimaono led St George Illawarra to the 2022 grand final before earning a call-up to the undefeated Jillaroos squad that took home World Cup glory.