The 20-year-old forward joined Chelsea from Barcelona on July 1, 2024, and leaves after making 29 competitive appearances for the London club across all competitions.
Guiu scored eight goals during his time at Chelsea before deciding that Leipzig offered the right opportunity for the next stage of his development.
"Joining RB Leipzig is exactly the right step for me," Guiu said. "The club made a real effort to bring me here and, in our talks, gave me a clear idea of the role I can play in the team.
"RB Leipzig have shown time and again that young players can develop here at the very highest level. RBL are also an ambitious club with high aspirations in every competition.
"I want to play my part in achieving those goals while continuing to improve every day."
Leipzig's managing director for sport, Marcel Schafer, believes Guiu's pace, intensity and work rate make him a natural fit for the club.
"Marc is a very good fit for our RB DNA with his intensity, pace and incredible work rate," Schafer said.
"He's relentless in his work without the ball, while he's also a real presence in the box and is always looking to get at goal.
"Despite being only 20, he already has experience at the highest level and in the Champions League."
Schafer revealed that Leipzig had followed Guiu's progress for some time before securing his signature.
"We've been in contact with him for a long time and have followed his development very closely, so we're delighted that he has chosen RB Leipzig," he said.
"We're convinced he has the quality and mentality to make an immediate impact, while he still has plenty of room to develop further."
