Czarnik joined the Chemistry Department at the Ohio State University as assistant professor in 1983. He later was promoted to associate professor. Czarnik worked at Ohio State University until 1993, when he was offered a position as Director of the Bio-Organic Chemistry group at Parke-Davis Research Laboratory in Ann Arbor, Michigan. Czarnik was the founding editor of ACS Combinatorial Science (formerly Journal of Combinatorial Chemistry), an academic journal published  by the American Chemical Society. 
In April 1998, Czarnik co-founded Illumina, Inc., a biotechnology company now traded on NASDAQ and specializing in sequencing, genotyping and gene expression, with David Walt, John Stuelpnagel, Larry Bock, and Mark Chee. Czarnik served as Illuminas chief scientific officer (CSO) until 2000. He was terminated from his position of CSO and later filed a wrongful termination lawsuit. The Court ruled in Czarniks favor, but the company appealed. The appeal court sustained the lower court verdict but in 2005 reduced the punitive damage ordered by the jury. Czarnik later filed a patent law case in the United States District Court for the District of Delaware, alleging four counts against his former employer, including reputational harm for correction of named inventor under 35 U.S.C. § 256.
In 2001, Czarnik was recruited by Sensors for Medicine and Science, Inc., where he served as chief scientific officer. Since 2003, Czarnik has co-founded a number of biotechnology companies including Deuteria Pharmaceuticals LLC and Protia LLC.
Czarnik is a founder of RenoCares, a charity that provides support to alcohol and drug addicts convicted of misdemeanors in the form of financial aid for rehabilitation treatment, counseling, and psychological services. The organization is managed by the Community Foundation of Western Nevada. Since 2016, annual Czarnik Awards are given for exceptional work in the area of chemosensors at the International Conference on Molecular Sensors and Molecular Logic Gates (MSMLG). In 2007, Czarnik  took part as an executive producer of Electric Heart: Don Ellis, a documentary about Don Ellis, an American jazz musician.