After Cleveland annexed Ohio City in 1854, the city’s new west side wanted their own high school on their side of the Cuyahoga River, but struggled to find a way around a state law that permitted only one public high school to exist in Cleveland. A. G. Hopkinson, principal of a school in the former Ohio City, came up with the idea that building a branch high school on the west side would not violate the state law. City council was persuaded and in 1855 passed legislation creating east and west divisions of Central High School and the west division later became known as West High School. 

The west side’s school age population continued to grow rapidly in the last two decades of the nineteenth century and in 1900 the city built a second west side high school, Lincoln High School. In 1970, West High merged with Lincoln High, creating Lincoln-West High School, a new high school with its campus on West 30th Street in the Clark-Fulton neighborhood. 

In December 2014, initial discussion began at a meeting between CMSD's CEO, Eric Gordon, and the MetroHealth System's CEO, Dr. Akram Boutros. A vision emerged that aligning a high school program with the MetroHealth System would offer significant benefits to students. A collaborative work team comprised of CMSD and MetroHealth staff was charged to investigate the potential of designing a high school program that would be aligned with MetroHealth. 

In Spring 2015, CMSD was awarded its second $3 million dollar Carnegie Opportunity by Design grant. Two new schools would be designed to replace the traditional program at Lincoln-West. One of the schools would be a Science and Health academy with MetroHealth as its signature partner taking full advantage of the varied career pathways contained within the hospital system. Planning for the school utilized the Portfolio design process, beginning with a community advisory committee to create the school's guiding principles and portrait of a graduate. Additionally, during this time, MetroHealth and CMSD staff met to develop a partnership agreement and work through logistical challenges of crafting a school site within a hospital. 

Lincoln-West School of Science and Health is a mastery-based, year-round school that opened in July 2016.