In 1938,  a few Protestant families living in a tiny settlement known as La Mesa, on the eastern outskirts of the city of Albuquerque, began meeting regularly for Sunday school in the original La Mesa School, a one-room building at the corner of Louisiana and Copper. A Presbyterian minister, Rev. David Reiter, of the Presbyterian Board of National Missions, helped organize a class and lead worship for a group of about 20 adults and children. It was named the La Mesa Community Sunday School.

Two years later, when a four-room school was built at Copper and Española, the rapidly growing Sunday School class moved with it and continued to meet at La Mesa Elementary School until 1945. Several denominations were interested in establishing a church in the community and sent delegations to have conversations with the class about affiliation. A vote was taken and a decision made to become a Presbyterian congregation. There were 83 signatures on petition to Rio Grande Presbytery on November 9, 1942, requesting the organizing of a congregation. In 1942, Rev. Morton Young was appointed as organizing pastor and on February 4, 1944, the La Mesa Community Presbyterian Church was formally organized with 32 charter members. 

In 1942, the church had been given land on the northwest corner of Española and Copper. Purchased with a loan from the Board of National Mission, lumber salvaged from barrack buildings of a Civilian Conservation Corps camp in the Jemez Mountains was used to erect an all-purpose center in 1945.  Rev. Young left in December of 1946 and was followed by short pastorates of Rev. D. Lennington and Rev. Lane C. Findley. In 1948, the church called Rev. William Dalton to be its first full-time pastor. The sanctuary was constructed during his tenure. When he retired in 1950, the church called Rev. Harry Summers as pastor. Under his vigorous leadership, the church grew from 68 members to over 500.

In 1964, after a fourteen-year tenure, Rev. Summers accepted a call to become the first Executive Secretary of the New Mexico Conference of Churches. Rev. Stewart Coffman was installed in 1966. Rev. Coffman guided the church to explore new ways of worship and congregational life, as well as expanding the church's mission efforts. A used pipe organ given by Immanuel Presbyterian Church was installed in the sanctuary in 1965. A bell was purchased from a congregation in Missouri for the bell tower in 1967.

Rev. Coffman left La Mesa in 1969. Rev. Gary J. Looman began his pastorate which lasted until the spring of 1978. The church expanded its ecumenical work and adult Bible study during his pastorate.

The Rev. Howard Paul was installed as pastor in  January of 1979. Under his leadership, La Mesa became more involved in the neighboring community and in work with the Presbytery of Santa Fe and the Synod of the Southwest. He helped organize a celebration of the 50th anniversary of the church in February of 1994. He also guided the congregation through a discernment process in the late 1980's as to the future of the church, considering whether to remain and continue to serve the La Mesa neighborhood or to move the church to another part of the city. The decision was made to remain and to expand the facility to increase its usefulness to the congregation and the community. In May of 1994, groundbreaking took place for a major expansion. The old office, parlor, and library were demolished and a new large Fellowship Hall, parlor/library, office area, and a large kitchen with commercial appliances were built.

Rev. Paul retired in November of 1994 after a 15 year pastorate. The Rev. Bill Scholes was interim pastor and helped in the transition of moving into the new facility. In March of 1996, the Reverends Richard and Kathryn Pyke were called to serve as co-pastors. They brought new energy to the programs and worship of the church. They concluded their service in the fall of 1998. 

The Rev. Trey Hammond began his pastorate at La Mesa in October of 1999. He had been serving as the Coordinator for Urban Ministry of the national staff of the Presbyterian Church(USA), following 15 years of service in urban churches in the Dallas area. During his tenure the church has continued to deepen its connections with the local community. Those efforts include a growing partnership with La Mesa Elementary School, the La Mesa Arts Academy, and the La Mesa Neighborhood Garden Park. 

In addition, La Mesa has been a leader in Albuquerque Interfaith, a community organizing effort, and helped the start-up of a men's program and shelter for men experiencing homelessness called the Albuquerque Opportunity Center in 2004. A major renovation of the building took place in 2012 that included a major rehab of the Learning Center, previously called the Christian Education building, and repairs to  the organ. The La Mesa Arts Academy was initiated in 2006, a partnership with La Mesa Elementary School to provide free after-school art, music, dance, and drama classes. The La Mesa Neighborhood Garden Park had a groundbreaking in 2013.