Representatives of the NFL outfit will travel to Leeds to discuss important aspects of the club's business.
Leeds managing director David Haigh told the club's official website: "This is a strategic partnership and we're looking forward to working closely with the 49ers.
"They are a worldwide brand, and we'll be discussing all aspects of our business; marketing, ticketing, merchandising, and commercial opportunities, and hopefully tapping into and sharing knowledge with them."
Chief operating officer of the 49ers Paraag Marathe also said: "The 49ers are very excited about the prospect of partnering with Leeds United, a club with an international following as well as great history and tradition.
"We look forward to sharing best practices with Leeds United and providing them with our perspective on the sports industry. This is an exciting opportunity for us to link up with an English football club and learn from each other."