He previously owned a Mediterranean-style house in Palm Beach, Florida, designed by famed American Architect Marion Sims Wyeth. The house, built in 1924, features a west-facing facade that has been designated a historic landmark since 1990. In June 2010, Stryker expanded the property where the house sits by purchasing an adjoining ocean-access lot that included the former residence of Jimmy Buffett and Jane Buffett for $18.5 million.

Stryker was born in Kalamazoo, Michigan. He is the youngest grandchild of Homer Hartman Stryker, founder of the medical supply company Stryker Corporation. Jon's Father, Lee Stryker, died in an airplane crash in 1976.

Stryker earned a Bachelor of Arts degree in biology from Kalamazoo College in 1982. He now serves on the college's Board of Trustees and was the recipient of the college's 2010 Distinguished Service Award. He also has a Master of Architecture degree from the University of California at Berkeley.

In 2000, Stryker established the Arcus Endowment at the UC Berkeley College of Environmental Design. The endowment supports a wide range of critical and creative activities at the intersection of LGBT issues and urban design and planning. In 2010, Stryker gave an additional $1 million to create a new chair position at the college named the Arcus Chair in Gender, Sexuality and the Built Environment. In 2016, Stryker was named the inaugural recipient of the college's Catherine Bauer Wurster Award for Social Practice. The award honors the legacy of Catherine Bauer Wurster and recognizes the significant achievements of a CED alumnus toward advancing social justice, environmental conservation, and fair urban development.

Stryker also owns multiple properties in his native Kalamazoo, and is credited with built-space revitalization efforts in the city. He unknowingly purchased the commercial building that once housed his grandfather's Orthopedic Frame Co., which eventually became Stryker Corp., before learning of the building's origins in 2003.

The Coalition for Progress paid for significant advertising in the 2006 Michigan gubernatorial election in support of Jennifer Granholm, who was re-elected as Governor of Michigan over Republican opponent Dick DeVos.

He briefly owned an apartment in the Time Warner Center in New York City's Columbus Circle before selling it 2007.

He was awarded the Creating Change Award by the National LGBTQ Task Force in 2008.

In 2009, Stryker's Arcus Foundation awarded a $200,000 planning grant and a $2.1 million project grant to Kalamazoo College to develop a social leadership center on campus. The Arcus Foundation also donated $5 million to cover the construction costs of the 10,000-square-foot building, now called the Arcus Center for Social Justice Leadership. In January 2012, Stryker's foundation awarded a $23 million endowment grant to support the center's operations and programming into the Future. The endowment was the largest donation in the college's 182-year history and one of the largest given to any undergraduate institution in the United States for a social justice purpose. Opened in 2014, the center’s mission is to support the pursuit of human rights and social justice by developing emerging Leaders and sustaining existing Leaders in the field of human rights and social justice.

For his efforts, Stryker received Kalamazoo College's 2010 Distinguished Service Award, which goes to alumni who have made exceptional personal contributions to the college.

In August 2012, Stryker donated $325,000 to the nonprofit group Freedom to Marry Minnesota, which helped to organize the defeat of a referendum that would have placed a state constitutional ban on same-sex marriage in Minnesota. In 2013, Minnesota became the 12th state to legalize same-sex marriage in the United States.

Stryker maintains a home in Garrison, New York, along the Hudson River. In June 2013, Stryker purchased the 129-acre property and placed it under a conservation easement to protect against any Future development of the riverfront land. The property’s parking area and extensive network of trails, including on-foot access to the Hudson River, is managed by the Open Space Institute and is open to the public, with the exception of a 21-acre residential area.

He received the 2014 Global Vision Award from Immigration Equality, a U.S.-based nonprofit organization that provides legal representation to LGBT and HIV-positive asylum seekers, detainees, and binational couples.

In 2015, Stryker donated 22-acres of land running along the west fork of Portage Creek in Kalamazoo, Michigan, to the Kalamazoo Nature Center. In addition to the land donation, Stryker committed to giving as much as $700,000 as part of a 2-to-1 matching grant that would go toward a proposed multi-phase restoration of the property and an environmental education facility on the site. As a condition of the donation, several conservation easements were placed on the property to ensure that the land remains protected and accessible to the public in perpetuity.

Stryker married his long-time partner Slobodan Randjelović in December 2016. He has two children from a previous marriage.

In 2017, Stryker was named a Patron of Nature by the International Union for Conservation of Nature.

Stryker also makes contributions in support of the college’s study abroad programs and enrollment diversity efforts. In 2008, he established a $5.6 million grant to fund the tuition and financial support of 50 Posse Scholars from the Los Angeles Unified School District. The grant, which supported the enrollment of 10 Posse Scholars in five consecutive academic classes at Kalamazoo College, was made in partnership with the Posse Foundation, a national organization that pairs high-performing public high school students from underrepresented groups in higher education with full, four-year academic scholarships at colleges and universities throughout the country. In 2001, Stryker made a $5 million grant in support of the college’s highly ranked study abroad programs.